Influence of the environment and probes on rapid DNA sequencing via transverse electronic transport

Abstract

We study theoretically the feasibility of using transverse electronic transport within a nanopore for rapid DNA sequencing. Specifically, we examine the effects of the environment and detection probes on the distinguishability of the DNA bases. We find that the intrinsic measurement bandwidth of the electrodes helps the detection of single bases by averaging over the current distributions of each base. We also find that although the overall magnitude of the current may change dramatically with different detection conditions, the intrinsic distinguishability of the bases is not significantly affected by pore size and transverse field strength. The latter is the result of very effective stabilization of the DNA by the transverse field induced by the probes, so long as that field is much larger than the field that drives DNA through the pore. In addition, the ions and water together effectively screen the charge on the nucleotides, so that the electron states participating in the transport properties of the latter ones resemble those of the uncharged species. Finally, water in the environment has negligible direct influence on the transverse electrical current.

FIGURE 1

Schematic of a nanopore (dark gray) with embedded electrodes (light gray) attached to the edges of the pore. The electrodes are used to inject a current through the nucleotides in the direction transverse to the backbone. The electronic signature can then be used to sequence the DNA.

FIGURE 2

Current, at a bias of 0.1 V, as a function of time for poly(A)₁₅, as (a) it is propagating through a pore with two electrodes without a stabilizing field, and (b) when the driving field is turned off at a time (indicated by the dashed line in a) while a base is aligned in between the electrode pair. Solid vertical line in panel a indicates the time at which the DNA starts propagating through the pore. The transverse electric field is included in the simulations for panel b. Δt represents a finite inverse bandwidth.

FIGURE 3

Top graph shows the probability distributions, assuming instantaneous measurements, of currents at a bias of 0.1 V for poly(X)₁₅, where X is A/T/C/G for the solid black, dash-dotted black, dotted gray, dashed gray curves, respectively. The thin lines show the actual current intervals used for the count, whereas the thick lines are an interpolation. After the driving electric field is turned off, the system is left to equilibrate for 200 ps before samples are taken. Each distribution is made up of 1200 samples, each taken with a 1-ps interval. The bottom graph again shows the probability distributions, but now with the assumption that each measurement is time averaged in between each sample. The solid/dashed-dotted line assumes that the distributions in the top graphs are sampled 100/1000/10⁷ times for each new data point.

FIGURE 4

Probability distributions of the conductance for varying stabilizing fields for poly(A)₁₅. Leftmost curve labeled “unaligned” corresponds to the completely unstabilized case as shown in Fig. 2 a, whereas other curves correspond to various stabilizing fields when the driving field is turned off. The symbol 0 V corresponds to the case in which the base is aligned in between the electrode, but there is no stabilizing field.

FIGURE 5

Current, at a bias of 0.1 V, as a function of time for poly(G)₁₅, for a single guanine base stabilized in between the electrodes by the transverse electric field, with (solid black curve) and without (dashed gray curve) water included in the current calculation.