We have previously demonstrated that a nanometer-diameter pore in a nanometer-thick metal-oxide-semiconductor-compatible membrane can be used as a molecular sensor for detecting DNA. The prospects for using this type of device for sequencing DNA are avidly being pursued. The key attribute of the sensor is the electric field-induced (voltage-driven) translocation of the DNA molecule in an electrolytic solution across the membrane through the nanopore. To complement ongoing experimental studies developing such pores and measuring signals in response to the presence of DNA, we conducted molecular dynamics simulations of DNA translocation through the nanopore. A typical simulated system included a patch of a silicon nitride membrane dividing water solution of potassium chloride into two compartments connected by the nanopore. External electrical fields induced capturing of the DNA molecules by the pore from the solution and subsequent translocation. Molecular dynamics simulations suggest that 20-basepair segments of double-stranded DNA can transit a nanopore of 2.2 x 2.6 nm(2) cross section in a few microseconds at typical electrical fields. Hydrophobic interactions between DNA bases and the pore surface can slow down translocation of single-stranded DNA and might favor unzipping of double-stranded DNA inside the pore. DNA occluding the pore mouth blocks the electrolytic current through the pore; these current blockades were found to have the same magnitude as the blockade observed when DNA transits the pore. The feasibility of using molecular dynamics simulations to relate the level of the blocked ionic current to the sequence of DNA was investigated.

We have produced single, synthetic nanometer-diameter pores by using a tightly focused, high-energy electron beam to sputter atoms in 10-nm-thick silicon nitride membranes. Subsequently, we measured the ionic conductance as a function of time, bath concentration, and pore diameter to infer the conductivity and ionic mobility through the pores. The pore conductivity is found to be much larger than the bulk conductivity for dilute bath concentrations, where the Debye length is larger than the pore radius, whereas it is comparable with or less than the bulk for high bath concentrations. We interpret these observations by using multiscale simulations of the ion transport through the pores. Molecular dynamics is used to estimate the ion mobility, and ion transport in the pore is described by the coupled Poisson-Nernst-Planck and the Stokes equations that are solved self-consistently for the ion concentration and velocity and electrical potential. We find that the measurements are consistent with the presence of fixed negative charge in the pore wall and a reduction of the ion mobility because of the fixed charge and the ion proximity to the pore wall.ion conduction ͉ nanopore ͉ nanostructured materials N anometer-diameter pores formed by proteins are prevalent in biology where they are used to regulate the flow of ions and molecules through the otherwise impermeable cell membrane. Even though the structure is known with atomic precision in some cases, there does not seem to be a simple relationship between the pore geometry and the conductivity (1). This difficulty may be due to the nonuniform, high concentration of charge in the pore (2).As a first step toward understanding the conductivity, we produced synthetic pores ranging in diameter from 1 to 3.2 nm in ultra-thin silicon nitride (Si 3 N 4 ) membranes and measured the ionic conductance as a function of time and electrolyte concentration to infer the conductivity and ionic mobility. This work measures the conductance through pores with radii comparable with the van der Waals radius of an ion (3-5). Similar claims by Siwy and Fuliński (6) that rely on the conductance through a single pore to estimate the pore diameter are unreliable, because conductance does not scale with the diameter. Like previous work in nanofiltration membranes that contain ensembles of pores with varying diameter (7), we find that the pore conductivity associated with a single pore is found to be much larger than the bulk conductivity for dilute electrolyte concentrations, where the Debye length is larger than the pore radius, whereas it is comparable with or less than the bulk for high concentrations. These observations are also consistent with a recent report by Stein et al. (8) of ion transport in silica channels Ͼ70 nm wide that is governed by surface charge. To interpret our observations, we use multiscale simulations of the ion transport through the pores. Molecular dynamics (MD) is used to estimate the ion mobility, and ion transport in the pore is described by the coupled Poisson-N...

Each species from bacteria to human has a distinct genetic fingerprint. Therefore, a mechanism that detects a single molecule of DNA represents the ultimate analytical tool. As a first step in the development of such a tool, we have explored using a nanometer-diameter pore, sputtered in a nanometer-thick inorganic membrane with a tightly focused electron beam, as a transducer that detects single molecules of DNA and produces an electrical signature of the structure. When an electric field is applied across the membrane, a DNA molecule immersed in electrolyte is attracted to the pore, blocks the current through it, and eventually translocates across the membrane as verified unequivocally by gel electrophoresis. The relationship between DNA translocation and blocking current has been established through molecular dynamics simulations. By measuring the duration and magnitude of the blocking current transient, we can discriminate single-stranded from double-stranded DNA and resolve the length of the polymer.

We have explored the electromechanical properties of DNA on a nanometer-length scale using an electric field to force single molecules through synthetic nanopores in ultrathin silicon nitride membranes. At low electric fields, E < 200 mV/10 nm, we observed that single-stranded DNA can permeate pores with a diameter >/=1.0 nm, whereas double-stranded DNA only permeates pores with a diameter >/=3 nm. For pores <3.0 nm diameter, we find a threshold for permeation of double-stranded DNA that depends on the electric field and pH. For a 2 nm diameter pore, the electric field threshold is approximately 3.1 V/10 nm at pH = 8.5; the threshold decreases as pH becomes more acidic or the diameter increases. Molecular dynamics indicates that the field threshold originates from a stretching transition in DNA that occurs under the force gradient in a nanopore. Lowering pH destabilizes the double helix, facilitating DNA translocation at lower fields.