An Accurate DNA Sensing and Diagnosis Methodology Using Fabricated Silicon Nanopores

Nanopore-based biomolecular sensing is an emerging nanotechnology which relies on the ability to measure changes in ionic conductance of single nanoscale pores as biomolecular analytes are driven through them, one at a time, by an applied electric field. Nanopores constructed from self-assembled proteins as well as using silicon-based fabrication techniques have been demonstrated to allow sizing and identification of DNA, RNA, proteins, and other biomolecules many times faster than with current technology. Despite the potential of nanopore sensing to produce "next generation" biomolecule analysis devices, its current demonstrations are based on the use of a simple dc stimulus across the nanopore. As a result, the resolution obtained is insufficient for many practical applications. In this paper, we report a novel diagnosis methodology for nanopore sensors based on optimization of a generalized electrical stimulus and a microscopic model of the biomolecule transport process. This methodology is applied to analyze the size distribution of an arbitrary mixture of DNA strands, which is a critical step in DNA sequencing. A transport model for long polymers in nanopores is built and parameterized to reproduce existing experimental data. The electrical stimulus is optimized "on-the-fly" using the model, to obtain a significant increase in the sizing resolution for any given range of DNA sizes and hence a clear identification of all sizes of DNA in the mixture. Hence, it is proposed that nanopore-based DNA sensing can be advanced significantly incurring no (or minimal) hardware overhead, by a combination of optimized stimuli and microscopic transport modeling