DNA Sequencing Based On Physical Properties at Single Nucleotide Resolution

Abstract

To realize such objectives as genomic medicine, it is required to develop economical and fast methods for DNA sequencing. In this paper, a novel approach is developed to signi cantly improve the e ciency of DNA sequencing based on physical di erences between nucleotides. Here, it is claimed that the reason for the rather low resolution of sequencing based on physical di erences is the extremely nonlinear and complex dynamics of DNA, making DNA translocation with respect to detectors highly dependent on initial conditions and environmental disturbances. In various sequencing methods, the position and orientation of nucleotides are di erent at the detection time. At a low signal-to-noise ratio, di erent dynamics of nucleotides make it di cult to detect slight di erences in the physical properties of DNA bases. This claim is con rmed by designing a sequencing nanodevice in which the motion of a stretched single-stranded DNA (ssDNA) is constrained in such a way that the axis of ssDNA backbone is xed and each nucleotide lies on a xed plane at the detection time. Further, nonlinear e ects of ssDNA and the interactions of detectors are reduced as low as possible. Results of molecular dynamics indicate that speci c and distinct signals of each type of nucleotide will be generated under constrained conditions.