We plan to build on our recently published work on DNA translocation through graphene nanopores (Merchant et al., Nano Lett. 10, 2915) and other preliminary results we describe in this application, to develop a DNA sensing technology based on measuring the current fluctuations of a graphene nanoribbon (GNR) as a single-stranded DNA molecule translocates through a pore in that ribbon. This geometry is anticipated to exhibit large electrical current changes for each nucleotide base due to the unique electrostatic potential associated with each nucleotide. These potentials modulate the charge density in the narrow ribbon, altering the corresponding GNR current levels. In contrast to approaches which measure tunneling current through the DNA molecule, where experimentally reported conductance differences are on the order of 6 pS (Chang et al., Nano Lett 10, 1070), the proposed GNR is continuous, with a large in-plane conductance. Base-to-base conductance differences are predicted to be on the order of 1-10 mS (Nelson, et al., Nano Lett. 10, 3237). Graphene defects and scattering effects are likely to lower the practical device conductance, but scaling these predictions based on reported GNR studies suggest that base-to-base conductance differences of 1 ?S could be achieved. The extra noise incurred by measuring at significantly higher bandwidth can be tolerated because the desired signals are so large. We anticipate that single-base resolution will be achievable at currently reported DNA translocation speeds. This eliminates the need for custom high-speed ultralow noise electronics, as many off-the-shelf photodiode amplifiers for fiber- optics are designed for these current and bandwidth ranges. It also removes the need to slow down or constrain the DNA molecule as it translocates, since the measurement speed is high enough to prevent Brownian fluctuations of the molecule from blurring the GNR signal.
The aims of our proposed research are as follows: 1. Fabricate atomically-thin, few-nm wide GNR devices suitable for DNA sequencing 2. Characterize the transverse electrical response of atomically-thin GNRs to each of the four nucleotides 3. Develop this sensing mechanism into an ultrafast sequencing (>1 megabase/sec), and demonstrate the sequencing of plasmid DNA molecules.

Public Health Relevance

This research aims to achieve much faster and lower-cost DNA sequencing with the development of a nanometer-sized electronic sensor constructed from an atomically-thin, carbon sheet known as graphene. It will enable major improvements in the understanding, diagnosis, treatment and prevention of disease, by allowing us to determine the underlying genetic causes and symptoms, detect these rapidly and accurately in patients, and treat them appropriately.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HG006313-03
Application #
8531313
Study Section
Special Emphasis Panel (ZHG1-HGR-N (M2))
Program Officer
Schloss, Jeffery
Project Start
2011-08-15
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
3
Fiscal Year
2013
Total Cost
$417,403
Indirect Cost
$152,800
Name
University of Pennsylvania
Department
Physics
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Han, Gang Hee; Rodriguez-Manzo, Julio A; Lee, Chan-Woo et al. (2013) Continuous growth of hexagonal graphene and boron nitride in-plane heterostructures by atmospheric pressure chemical vapor deposition. ACS Nano 7:10129-38
Venta, Kimberly; Shemer, Gabriel; Puster, Matthew et al. (2013) Differentiation of short, single-stranded DNA homopolymers in solid-state nanopores. ACS Nano 7:4629-36
Saha, Kamal K; Drndic, Marija; Nikolic, Branislav K (2012) DNA base-specific modulation of microampere transverse edge currents through a metallic graphene nanoribbon with a nanopore. Nano Lett 12:50-5
Rosenstein, Jacob K; Wanunu, Meni; Merchant, Christopher A et al. (2012) Integrated nanopore sensing platform with sub-microsecond temporal resolution. Nat Methods 9:487-92