We plan to explore the feasibility of sequencing a DNA molecule using a revolutionary type of silicon integrated circuit that incorporates a nanopore mechanism with a molecular trap. The essential component is a single, nanometer-diameter pore in a robust, nanometer-thick membrane formed from a Metal Oxide Semiconductor (MOS) capacitor. To sequence the molecule, the voltage induced by the dipole moment associated with each base is measured using the electrodes on the capacitor as the DNA translocates through the pore. The 1 nm diameter of the pore is a key specification since it forces the unique dipole moment associated with each base to be nearly transverse to electrodes during a translocation, while minimizing thermal fluctuations and excluding most of the water. Another crucial specification is the thickness of the SiO2 insulator separating the electrodes forming the capacitor. The spatial resolution for sequencing is essentially determined by the SiO2 thickness. With a 1 nm diameter pore and a 0.7nm thick oxide, we expect to be able to measure the electrical signal associated with a single base spanning the insulator during a translocation. To facilitate signal recovery, we intend to trap the molecule during the translocation through the pore, forcing it to oscillate back-and-forth between the electrodes. The oscillation in the position of the DNA allows for narrow-band synchronous detection (lock-in techniques) to be used to improve the electrical signal-to-noise level without compromising the throughput and effectively averages out the noise associated with conformational changes in the DNA and the ion distribution. While we plan to fabricate and test an integrated circuit incorporating a nanopore-capacitor mechanism with a molecular trap and optimize it for sequencing a single molecule of DNA, at the same time we also plan to simulate the performance and test the theoretical resolution of the mechanism using molecular dynamics in conjunction with a self-consistent 3D Poisson solver. ? ?
| Timp, Winston; Comer, Jeffrey; Aksimentiev, Aleksei (2012) DNA base-calling from a nanopore using a Viterbi algorithm. Biophys J 102:L37-9 |
| Comer, Jeffrey; Ho, Anthony; Aksimentiev, Aleksei (2012) Toward detection of DNA-bound proteins using solid-state nanopores: insights from computer simulations. Electrophoresis 33:3466-79 |
| Kowalczyk, Stefan W; Wells, David B; Aksimentiev, Aleksei et al. (2012) Slowing down DNA translocation through a nanopore in lithium chloride. Nano Lett 12:1038-44 |
| Carr, Rogan; Comer, Jeffrey; Ginsberg, Mark D et al. (2011) Modeling Pressure-Driven Transport of Proteins through a Nanochannel. IEEE Trans Nanotechnol 10:75-82 |
| Mirsaidov, Utkur M; Wang, Deqiang; Timp, Winston et al. (2010) Molecular diagnostics for personal medicine using a nanopore. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2:367-81 |
| Aksimentiev, Aleksei (2010) Deciphering ionic current signatures of DNA transport through a nanopore. Nanoscale 2:468-83 |
| Maffeo, Christopher; Schopflin, Robert; Brutzer, Hergen et al. (2010) DNA-DNA interactions in tight supercoils are described by a small effective charge density. Phys Rev Lett 105:158101 |
| Timp, Winston; Mirsaidov, Utkur M; Wang, Deqiang et al. (2010) Nanopore Sequencing: Electrical Measurements of the Code of Life. IEEE Trans Nanotechnol 9:281-294 |
| Luan, Binquan; Aksimentiev, Aleksei (2010) Electric and Electrophoretic Inversion of the DNA Charge in Multivalent Electrolytes. Soft Matter 6:243-246 |
| Luan, Binquan; Aksimentiev, Aleksei (2010) Control and reversal of the electrophoretic force on DNA in a charged nanopore. J Phys Condens Matter 22:454123 |
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