DNA Sequencing via Transverse Transport


Massimiliano Di Ventra
Department of Physics, UCSD
January 12, 2006

Fast and low-cost DNA sequencing methods would usher in a real revolution in medicine. A person would have his/her full genome sequenced so that drugs could be tailored to his/her specific illness; doctors would know in advance patients’ likelihood to develop a given ailment; cures to major diseases could be found faster. However, this dream of “personalized medicine” is hampered today by the still high costs and slow DNA sequencing methods. It still costs at least $10 million to sequence 3 billion base pairs humans’ genomes over a 6 month period.

We are exploring a completely novel approach to sequencing that employs the translocation of ss-DNA into nanopores of few nanometers in diameter. During DNA translocation into the nanopore, electrical current would be injected in the transverse direction so that a unique signal is expected to be detected for each nucleotide. [1] The entire genome could be translocated in the pore in minutes at a cost of few thousand dollars, i.e. orders of magnitude faster and cheaper than present methods. While this approach is so far just a theoretical proposal [1], experimental groups in the country are working to make it a reality.

We are employing molecular dynamics simulations coupled to quantum-mechanical calculations of electrical current to explore the feasibility of this approach in experimentally realizable systems. The figures show a case in which 15 Adenine bases (a polynucleotide, represented in yellow and red) translocate through a solid-state b-Si3N4 nanopore (blue). The gray dots represent the atoms of two pairs of gold electrodes (the fourth gold electrode is not visible in the figure) placed in the pore so that electrical current can flow from one electrode to the opposite one. Two different currents (one blue and one red in the figure) from each pair of oppositely-placed electrodes are calculated as a function of time while the Adenine bases translocate (three snapshots of the translocation are shown). The analysis of these currents reveals the orientations of the bases in the pore.
These simulations are essential to guide experimentalists in the realization of fast and low-cost DNA sequencing methods as they provide detailed electronic and atomic information about the physical processes involved during transport of DNA in solid-state nanopores.

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Watch Sequencing of Human Genone movie (MPEG 19.5 KB) >>

Work supported by the NIH-National Humane Genome Research Institute.

[1] M. Zwolak and M. Di Ventra, “Electronic Signature of DNA Nucleotides via Transverse Transport”, Nano Lett. 5, 421 (2005).