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Nanopore technology for DNA sequencing

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Title: Nanopore technology for DNA sequencing
Author(s): Comer, Jeffrey R.
Director of Research: Aksimentiev, Aleksei
Doctoral Committee Chair(s): Chemla, Yann R.
Doctoral Committee Member(s): Aksimentiev, Aleksei; Schulten, Klaus J.; Stack, John D.
Department / Program: Physics
Discipline: Physics
Degree Granting Institution: University of Illinois at Urbana-Champaign
Degree: Ph.D.
Genre: Dissertation
Subject(s): molecular dynamics sequencing DNA sequencing nanopore nanopore sequencing bionanotechnology computer simulations force spectroscopy nucleic acids transmembrane transport Brownian dynamics
Abstract: The pursuit of inexpensive DNA sequencing lies at the interface between nanotechnology and biotechnology—where silicon nanopores, nanoscale electrodes, and self-assembled molecular structures are as common as restriction enzymes, fluorescence detection, and genetic engineering. The motivation for this pursuit stems from the promise that personalized genomic information can make health care safer, faster, and more effective. Beyond the realm of human health, inexpensive sequencing is poised to have lasting impacts for the whole of biology. However, the integration of nanotechnology with biotechnology raises many difficult and interesting questions. Computer simulations can assist in answering these questions by providing a means to “see” nanoscale events that cannot be imaged by any experimental method. In the development of nanopore devices for DNA sequencing, computation has played a key role in revealing how DNA behaves in the high electric field and confined geometry of a nanopore. In this dissertation, I describe my contribution to computational work for the development of nanopore-based sequencing technology. In simulations which have been corroborated by experiments, I have found that DNA adopts qualitatively different conformations in nanopores of different sizes and that nanopores of the appropriate geometry can be used to trap DNA and control its conformation. By developing a method that can provide millisecond-long current simulations with atomic resolution, I have determined conditions under which the sequence of this trapped DNA can be discriminated by ion current measurements.
Issue Date: 2010-08-20
URI: http://hdl.handle.net/2142/16812
Rights Information: Copyright 2010 Jeffrey Comer. Some portions Copyright 2010 Springer, Copyright 2009 Biophysical Society, Copyright 2008 Oxford University Press, Copyright 2008 American Chemical Society,
Date Available in IDEALS: 2010-08-20
Date Deposited: 2010-08
 

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