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Experiments and Statistical Analysis with DNA in Biological and Solid-State Nanopores

Abstract

Nanopores are a powerful tool for probing the structure of single molecules, such as a strand of DNA. Acquiring as much information from the output signal generated by a nanopore is essential and ultimately dependent on several factors: offline estimation of pore parameters must be based on a good model; the amplifier that produces the ionic current signal from the pore must be low noise; nanopore experiments must be designed intelligently to properly test hypotheses; and---most importantly---the pore must be the right size. This thesis discusses these topics in four chapters. Chapter 1 discusses the design and validation of a nanopore circuit model used for conductance estimation. Chapter 2 presents research results characterizing noise and signal resolution of a novel patch-clamp amplifier and its implications on next-generation nanopore platforms. Chapter 3 discusses preliminary research on modeling the motion of double-stranded DNA for future experiments with dual solid-state nanopores. Finally, chapter 4, is preliminary research performed with the solid-state nanopore and discussing various pore dimensions. Ultimately, the reader will be presented with research that covers the biochemical and computational ends of nanopore technology and how they are used to obtain as much information as possible from a single current output.

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