Theory of high-resolution single molecule size determination using a solitary nanopore

This paper focus the theory of high-resolution single molecule size determination using a solitary nanopore. Nanopore based techniques were developed to detect, characterize, and quantify a wide-range of polymer types (e.g., single-stranded RNA/DNA, proteins, biowarfare agents, therapeutic agents against anthrax toxins, and chemically synthesized molecules). For example, it was recently shown that a single nanometer-scale pore permits the discrimination of polymers whose lengths differ by approximately 0.15 nm. We will discuss the physical basis of this method and its high resolving power.The nanopore, which is formed by the bacterial toxin alpha-hemolysin, forms spontaneously in a high-impedance planar lipid-bilayer membrane (Fig. 1). An electrostatic potential difference across the membrane forces ions in the surrounding aqueous electrolyte to flow through the pore. While in the pore, a single poly(ethylene glycol) molecule (PEG) reduces the ionic current (Fig. 2, left) in proportion to the polymer molecular mass. Each current transient is Gaussian distributed. A probability density function of the blockade mean values (Fig. 2, right) provides a size spectrum that easily resolves individual PEG monomers.