University of North Carolina at Chapel Hill Graduate School
Doi
Abstract
Nanofludic platforms such as solid-state nanopores and nanochannels enable the manipulation of DNA molecules and have the potential to be a low-cost and high-efficiency DNA sequencing device. DNA nanopore translocation is a process where DNA moves from one chamber to another through a nanopore. To get into the pore, the molecule entropy decreases and free energy increases. In order to thread the DNA throughout the pore, an electric bias is applied to overcome the entropic energy barrier. The occupation of DNA impedes the ion transport and creates a blockage current of which the amplitude and duration provide the information on the DNA sequence since different bases (or base pairs) can be discriminated through different magnitude of blockage. Mining DNA sequence from the electric current profile requires an accurate knowledge of the passage time of a given base along the molecule. Our model assumes that the translocation process at high fields proceeds too fast for the chain to relax, and thus the distribution of translocation times of a given monomer are controlled by the initial conformation of the chain (the distribution of its loops). The model predicts the translocation time distribution is determined by the distribution of initial conformation as well as by the thermal fluctuations to the conformation during the translocation process. Narrow nanochannels require high threshold electric fields to achieve DNA translocation, leading to short dwell times of DNA in these channels. Nano-funnels integrated with nano-channels reduce the free energy barrier and lower the threshold electric field required for DNA translocation. A focused electric field within the funnel increases the electric force on the DNA, compresses the molecule, and increases the osmotic pressure at the nano-channel entrance which facilitates the entry at lower electric fields. Besides controlling the speed of the molecule's movement, appropriately designed nano-funnels such as parabolic shaped ones can also function as tweezers that allow the trapping and stable control of the position of the DNA molecule. A combination of a series of nano-funnels devices enable a wider range of location and speed manipulation and can assist genome mapping and sequencing when equipped with base detector.Doctor of Philosoph
