Computational Proof-of-Concept of Next-Generation Nucleotide–Tunneling-Current-Based Nanopore Sequencing Devices
D. Sengupta, J. Jenkins, Z. Sikorski and S. Sundaram
CFD Research Corporation, US
nanopore DNA sequencing tunneling current
A complete knowledge of the DNA sequence of an individual can yield fundamental insight into disease diagnosis, treatment and possibly prevention. To date the most reliable method of determining a genetic sequence is through the use of the Sanger chain termination chemistry, however a typical mammalian sequence costs millions of dollars and requires many months for completion. Nanopore-based methods have come under intense investigation recently due to the promise of inexpensive ultra high-throughput sequencing of DNA, with an entire mammalian sequence being determined at a cost of under $1,000 (goal set forth by the National Human Genome Research Institute located at http://www.genome.gov). In practice, a voltage bias applied to a nanopore induces a charged, single stranded DNA molecule to translocate through the pore (Figure 1a). The sequence of the DNA is determined via modulation of the electrical properties, as the strand translocates through the nanopore. Several previous studies focused on measuring the change in ionic currents as the DNA translocates, however this signal was found to be too weak for practical purposes. An alternate method that has been proposed recently is to sequence DNA by placing nanowires at the pore entrance and monitoring the modulation of the local electron tunneling currents (Figure 1b).The primary model outcome will be I-V curves for isolated nucleic acids, as well as an assessment of near neighbor interactions in a single stranded DNA chain. Key innovations that mark this research include:•Use of realistic nucleic acid geometries taken from previous molecular dynamics simulations of DNA translating through nanopores (Jenkins, 2005).•Assessment of the effect of near neighbor nucleic acids on the conductance of an individual nucleic acid.•Optimization of the electrode placement and nanopore geometry to maximize the amplitude and variation in the nucleic acid conductances.The final result of this computation will be the I-V curves for the individual nucleotides for conformations commonly found in a nanopore, along with an assessment of the dependence of the I-V curves on the near neighbor nucleotides within a DNA strand and the magnitude of the near neighbor perturbation.
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Nanotech 2006 Conference Program Abstract