Distinguishing single DNA nucleotides based on their times of flight through nanoslits: a molecular dynamics simulation study

Brian R. Novak, Department of Mechanical and Industrial Engineering, and Center for Computation and Technology, Louisiana State University, Baton Rouge, Louisiana 70803, USA.
Dorel Moldovan
Dimitris E. Nikitopoulos
Steven A. Soper


Transport of single molecules in nanochannels or nanoslits might be used to identify them via their transit (flight) times. In this paper, we present molecular dynamics simulations of transport of single deoxynucleotide 5'-monophoshates (dNMP) in aqueous solution under pressure-driven flow, to average velocities between 0.4 and 1.0 m/s, in 3 nm wide slits with hydrophobic walls. The simulation results show that, while moving along the slit, the mononucleotides are adsorbed and desorbed from the walls multiple times. For the simulations, the estimated minimum slit length required for separation of the dNMP flight time distributions is about 5.9 μm, and the minimum analysis time per dNMP is about 10 μs. These are determined by the nature of the nucleotide-wall interactions, channel width, and by the flow characteristics. A simple analysis using realistic dNMP velocities shows that, in order to reduce the effects of diffusional broadening and keep the analysis time per dNMP reasonably small, the nucleotide velocity should be relatively high. Tailored surface chemistry could lead to further reduction of the analysis time toward its minimum value for a given driving force.