We propose to sequence DNA by harnessing the one-atom thickness (as thin as the separation between nucleotides) and electrical properties of graphene. A direct readout of the DNA sequence is possible by measuring the modulation of the current flowing through a single-layer graphene nanoribbon (GNR), induced by each base in a single-stranded DNA molecule as it passes through a nanopore (NP) in that GNR. This geometry is anticipated to exhibit large changes in the charge density and electrical current levels in the GNR for each nucleotide base translocating due to the unique electrostatic potential associated with each nucleotide. The major benefit of this approach is that the GNR operating currents (1-10 mA) are orders of magnitude higher than the signals in ionic-current-based sequencing, enabling much higher signal-to-noise ratio and sequencing speeds of 106 bases/s. Important feasibility tests have already been realized in our group. We tested 20 - 200 nm-wide single-layer GNRs with NPs at the GNR edges carrying up to 10 mA in 1 mM to 1M KCl solution at bandwidths as high as 100 MHz. We also developed a method to drill NPs without lowering the GNR conductance and observed correlated GNR and ionic signals during dsDNA translocation. 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. Optimize GNR device parameters and measurement conditions to achieve sequencing with an error rate less than 0.1% at 10 MHz bandwidth. 2. Demonstrate proof-of-principle multiplexing with ten GNRs on a single chip. 3. Develop the GNR nucleotide sensing mechanism towards an ultrafast, low cost DNA sequencing solution.
This research aims to achieve much faster and lower-cost DNA sequencing with the development of a nano- meter-sized electronic sensor constructed from an atomically-thin, carbon sheet known as graphene, shaped into a highly-conducting graphene nanoribbon. 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.
|RodrÃguez-Manzo, Julio A; Qi, Zhengqing John; Crook, Alexander et al. (2016) In Situ Transmission Electron Microscopy Modulation of Transport in Graphene Nanoribbons. ACS Nano 10:4004-10|