Identification of Single Nucleotides by a Tiny Charged Solid-State Nanopore

Discrimination of single nucleotides by a nanopore remains a challenge because of the minor difference among the four types of single nucleotides. Here, the blockade currents induced by the translocation of single nucleotides through a 1.8 nm diameter silicon nitride nanopore have been measured. It is found that the single nucleotides are driven through the nanopore by an electroosmotic flow instead of electrophoretic force when a bias voltage is applied. The blockade currents for the four types of single nucleotides are unique and differentiable, following the order of the nucleotide volume. Also, the dwell time for each single nucleotide can last for several hundred microseconds with the advantage of the electroosmotic flow, which is helpful for single nucleotide identification. The dwell-time distributions are found to obey the first-passage time distribution from the 1D Fokker–Planck equation, from which the velocity and diffusion constant of each nucleotide can be deduced. Interestingly, the larger nucleotide is found to translocate faster than the smaller one inside the nanopore because the larger nucleotide has a larger surface area, which may produce larger drag force induced by the electroosmotic flow, which is validated by molecular dynamics simulations