The technologies that make sequencing DNA fast, cheap and widely available have the potential to revolutionize bio-medical research and herald the era of personalized medicine. Being able to sequence human genomes for $1000 will enable comparative studies of variations between individuals in both sickness and health. Ultimately it can improve the quality of medical care by identifying patients who will gain the greatest benefit from a particular medicine, and those who are most at risk of adverse reactions. Nanopore-based sequencing technologies attempt to thread a long DNA molecule through a few nanometer wide nanopore and use physical differences between the four base types to read the sequence of bases in DNA. The two major potential benefits of nanopore sequencing are the high speed and the low price. Nanopore sequencing does not need slow and expensive chemistry, therefore electrical-only sequence readout can proceed at highest rates achievable by modern electronics. At present, the nanopore sequencing is still a promise - no single nucleotide resolution has as yet been achieved experimentally. It is very likely that the ability to localize a DNA molecule inside a nanopore with a single base resolution would provide a sufficient time for read-out electronics to determine the base type. We propose a nano-electro-mechanical device (DNA Transistor) capable of controlling the translocation of a single DNA molecule inside a nanopore with single nucleotide accuracy. This function is based on interaction of discrete charges, localized on phosphate groups along the backbone of a DNA molecule, with the externally controlled electric field confined inside the nanopore. The design of the DNA Transistor relies on well researched thin film deposition techniques from the semiconductor industry. The device is a stack of metal and dielectric layers, each a few atoms thin, with a nanopore penetrating through the stack. Voltage differences applied to the metal layers create a trap for the DNA molecule inside the nanopore. By pulsing these voltages, the controlled translocation of the molecule with single base resolution can in principle be achieved. IBM Research is uniquely positioned to implement the proposed idea. Our experimental effort will rely on in-house industry leading semiconductor device fabrication facilities. The experimental component of the effort will be complemented by a modeling and simulation component that will rely on in-house Blue Gene supercomputing capabilities. Our goal is to fabricate the DNA transistor and demonstrate its capability to translocate DNA molecules through the nanopore with single base resolution.

Public Health Relevance

IBM proposes the design, characterization and production of a nano-electro-mechanical device (the DNA Transistor) that forms the basis of a fast technology to sequence human genomes for $1000. The widespread availability of this technology will enable comparative studies of variations between individuals in both sickness and health. Ultimately it can improve the quality of medical care by identifying patients who will gain the greatest benefit from a particular medicine, and those who are most at risk of adverse reactions.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
1R01HG005110-01
Application #
7715089
Study Section
Special Emphasis Panel (ZHG1-HGR-N (M1))
Program Officer
Schloss, Jeffery
Project Start
2009-09-25
Project End
2012-08-31
Budget Start
2009-09-25
Budget End
2010-08-31
Support Year
1
Fiscal Year
2009
Total Cost
$556,622
Indirect Cost
Name
Ibm Thomas J. Watson Research Center
Department
Type
DUNS #
084006741
City
Yorktown Heights
State
NY
Country
United States
Zip Code
10598
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