Optimizing the Sensitivity of DNA Concentration Measurements using Nanopores

Abstract

difficult to imagine a physical mechanism by which mass would be the decisive molecular property determining the depth of block. Here, we show that it is, indeed, possible to achieve high-fidelity discrimination between leucine or isoleucine (MW=131 g/mol) linked to the C-terminus of a heptarginine carrier. We show that single-passage discrimination between these two isomers can be made to exceed 95% using optimized low-noise recording conditions and careful analysis of the complex resistive pulses characteristic of the aerolysin pore. Notably, we identify a low-frequency component of added current noise as the limiting factor in peptide discrimination and show that this may be significantly reduced by substitution of NO3-for Cl-in the recording electrolyte. (1)