Fluctuation tolerant read scheme for ultrafast DNA sequencing with nanopore device

A charge-integration read scheme has been developed for a solid-nanopore DNA-sequencer that determines a genome by direct and electrical measurements of tunneling current in a single-stranded DNA. Although the tunneling current varies depending on the translational and rotational movement of the DNA, the developed scheme cumulates charge at the parasitic capacitance of the nanopore device so that the base-types can be distinguished even under such noisy condition. A circuit simulation demonstrates that the scheme successfully distinguishes between each DNA base at the speed of 2.0 ms/base. The speed is roughly six orders faster than that of a conventional DNA sequencer. With another scheme which reads complementary base-pair simultaneously with two nanopores, the speed is further improved, and the human genome can be sequenced in only one day if 100 nanopore systems operate in parallel with the scheme.

[1]  B. Luan,et al.  Base-by-base ratcheting of single stranded DNA through a solid-state nanopore. , 2010, Physical review letters.

[2]  F. Collins,et al.  The Human Genome Project: Lessons from Large-Scale Biology , 2003, Science.

[3]  J. Bonfield,et al.  Finishing the euchromatic sequence of the human genome , 2004, Nature.

[4]  F. Collins,et al.  New goals for the U.S. Human Genome Project: 1998-2003. , 1998, Science.

[5]  Jin He,et al.  Electronic Signatures of all Four DNA Nucleosides in a Tunneling Gap , 2010, Nano letters.

[6]  M. Taniguchi,et al.  Identifying single nucleotides by tunnelling current. , 2010, Nature nanotechnology.

[7]  S. Turner,et al.  Real-Time DNA Sequencing from Single Polymerase Molecules , 2009, Science.

[8]  Takayuki Kawahara,et al.  Fluctuation Tolerant Charge-Integration Read Scheme for Ultrafast DNA Sequencing with Nanopore Device , 2012, IEICE Trans. Electron..

[9]  Bernard P. Puc,et al.  An integrated semiconductor device enabling non-optical genome sequencing , 2011, Nature.

[10]  Y. Pershin,et al.  Effect of noise on DNA sequencing via transverse electronic transport. , 2009, Biophysical journal.

[11]  Graham Bell,et al.  Phenotypic consequences of 1,000 generations of selection at elevated CO2 in a green alga , 2004, Nature.

[12]  Robert B. Hartlage,et al.  This PDF file includes: Materials and Methods , 2009 .

[13]  M. Ventra,et al.  Colloquium: Physical approaches to DNA sequencing and detection , 2007, 0708.2724.

[14]  M. Di Ventra,et al.  Influence of the environment and probes on rapid DNA sequencing via transverse electronic transport. , 2007, Biophysical journal.

[15]  Michelle D. Wang,et al.  Single-Molecule Studies Reveal Dynamics of DNA Unwinding by the Ring-Shaped T7 Helicase , 2007, Cell.

[16]  Timothy B. Stockwell,et al.  The Sequence of the Human Genome , 2001, Science.

[17]  Jin He,et al.  Identifying single bases in a DNA oligomer with electron tunnelling. , 2010, Nature nanotechnology.