DNA Sequencing Based On Physical Properties at Single Nucleotide Resolution

Abstract

To realize objectives such as genome-based medicine, it is required to develop economical and fast methods for DNA sequencing at single-nucleotide resolution. In this paper a novel approach is developed to significantly improve efficiency of DNA sequencing based on physical differences between nucleotides. 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 environmental disturbances. 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 slight 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 single-stranded DNA (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. Also nonlinear effects in ssDNA and detectors interactions are reduced as low as possible. Results indicate that under these constrained conditions, specific and distinct signal for each type of nucleotide will be generated.