Ramsey Research GroupThe University of North Carolina at Chapel Hill

Department of Chemistry

DNA Transport

When a DNA molecule is forced into a nanochannel the confinement imposed by the nanochannel walls results in its extension.  For nanochannel diameters below a macromolecule’s persistence length (~50 nm for double-stranded DNA) this extension approaches the molecule’s full contour length.  Confining macromolecules in sufficiently narrow nanochannels thus facilitates the resolution of specific regions along the molecule – for example, regions of highly methylated DNA. We are investigating the dynamics of DNA transport through nanofluidic channels.  Our focus has been on devices that are used in a continuous flow mode of operation, where DNA molecules are monitored as they are constantly driven through a single channel or channel array (Figure 1).

transport figure 1

Figure 1. (left) Scanning electron micrograph showing an array of 100-nm channels spanning a 50-µm gap between microchannels.  A voltage was applied across the array and fluorescently-stained DNA molecules were transported through the nanochannels. (right) Fluorescence image showing the rapid transport of a DNA molecule through a nanochannel in the array.

We have found that the process of pulling a DNA molecule into a nanochannel using an electric field results in significant extension of the DNA molecule. Throughout the course of the subsequent transport, the molecule relaxes towards an equilibrium, confinement governed extension length. In our experiments, this length is influenced by the constant force applied to the molecule in the electric field. Several parameters are affected by the degree of confinement (i.e., by the nanochannel diameter), including the threshold field needed to initiate transport, the degree of extension, and the electrophoretic mobility (Figure 2).

Transport Figure 3

Figure 2. (a) Schematic of DNA transport through a nanochannel array.  Series of stacked fluorescence images captured during DNA transport through a 100-nm nanochannel.  (b) The molecule’s length and the position of the center of mass were extracted from each image in the series. (c) The measured transport velocities were used to calculate DNA electrophoretic mobilities in nanochannels of various sizes.  As the nanochannel diameter decreased, mobility decreased from the value measured in the non-confining microchannels.

We have also fabricated devices containing intersecting fluidic elements that enable electrical detection of molecules and increased control of DNA transport.  By measuring a transverse ionic current in a crossed-nanochannel device, we were able to detect the transport of unlabeled DNA molecules through a nanofluidic channel (Figure 3).

Transport Figure 3

Figure 3. A device containing intersecting, orthogonal nanochannels allows the non-fluorescence-based detection of DNA molecules during their transport through a nanochannel.  The ionic conductance is measured through the transverse nanochannel and current perturbations correspond to the passage of DNA molecules through the nanochannel intersection.

The incorporation of intersecting nanochannels and fluidic elements such as three-dimensional nanofunnels has more recently enabled us to tightly control DNA transport and add functionality to nanofluidic devices.  We are currently directing our efforts toward the deft manipulation of larger DNA fragments, approaching the size of chromosomes.


L. D. Menard, C. E. Mair, M. E. Woodson, J. P. Alarie and J. M. Ramsey (2012) A device for performing lateral conductance measurements on individual double-stranded DNA molecules. ACS Nano 6, 9087-9094.

L. D. Menard and J. M. Ramsey (2013) Electrokinetically-driven transport of DNA through focused ion beam milled nanofluidic channels. Anal. Chem. 85, 1146-1153.