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A Novel Approach in DNA Sequencing Based on Physical Differences of Nucleotides

Ebadi Jalal, Farhad | 2015

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 48153 (08)
  4. University: Sharif University of Technology
  5. Department: Electrical Engineering
  6. Advisor(s): Nejat Pishkenari, Hossein; Meghdari, Ali; Vossoughi, Gholamreza
  7. Abstract:
  8. With the continued improvement of sequencing technologies, the prospect of genome-based medicine is now at the forefront of scientific research. To realize this potential, however, a revolutionary sequencing method is needed for the cost-effective and rapid interrogation of individual genomes. Generally there are key factors in the definition and evalution of sequencing methods: 1-read length, 2-throughput, 3-read accuracy, 4-read depth, and 5-cost per base. The purpose of developing new sequencing methods is making better at least one of these factors. In order to reach the goal of rapid and low-cost sequencing method, one cannot rely only on current techniques. Improvements of current technology face both fundamental and practical limitations, such as a small¬ read-length limit using electrophoresis. In the other hand microfabrication technology has made it possible to make a variety of micro- and nanofluidic devices for biochemical and biophysical analysis. In this thesis a novel approach to sequence DNA is developed which significantly improves most key factors mentioned above. Here it is claimed that the reason for rather low resolution of sequencing based on physical differences, is the extremely nonlinear and complex dynamics of the DNA; it causes great dependence of DNA translocation with respect to detectors on initial conditions and external excitation. In various sequencing, the position and orientation of nucleotides would thus be different in detection time. By decreasing signal-to-noise ratio, these different dynamics of nucleotides prevent detecting poor differences in physical properties of DNA bases. The correctness of this claim is verified by designing a sequencing nanodevice in which motion of a stretched ssDNA is constrained in such a way that axis of ssDNA backbone is fixed and in detection time each nucleotide lies in a fixed plane. Results from molecular dynamics indicate that under these constrained conditions specific and distinct signal for each type of nucleotide can be achieved
  9. Keywords:
  10. Physical Properties ; Single Strand DNA ; Nano Channel ; Nanotube Arrays ; DNA Sequencing

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