ABSTRACT

In the past 20 years, nanopores have evolved into powerful and

versatile probes for the world of single biomolecules, allowing

scientists to detect them and discriminate between them with

remarkable precision with relatively lightweight instruments. The

basic concept follows the same idea as the Coulter counter [Coulter

(1953)], but scaled down to singlemolecules: The analyte of interest,

dissolved in an electrolyte solution, appears as a modulation of the

ion current when it crosses a small pore. The attention attracted

by these experiments would likely have been far smaller, if-only 4

years after seminal experiments had been published [Branton et al. (1996)]—it had not been found that solely based on the current

signal it is possible to distinguish single-stranded DNA (ssDNA)

molecules by their bases [Meller et al. (2000)]: The current blockade e.g., of poly(dC) was less pronounced than that of poly(dA). The

idea to build a nanopore-based read-out device, which sequentially

reads single DNA molecules, was born. This great leap for science

and medicine is not yet made, although many theoretical and

experimental hurdles that accompany this enterprise have been

cleared. Although DNA sequencing is themost prominent focal point

of ongoing research, also other applications in analytic chemistry or

clinical diagnosis are of significant interest.