The detection of organic molecules is important in many areas, including me
dicine, environmental monitoring and defence(1-5) Stochastic sensing is an
approach that relies on the observation of individual binding events betwee
n analyte molecules and a single receptor(6). Engineered transmembrane prot
ein pores are promising sensor elements for stochastic detection(6), and in
their simplest manifestation they produce a fluctuating binary ('on/off')
response in the transmembrane electrical current. The frequency of occurren
ce of the fluctuations reveals the concentration of the analyte, and its id
entity can be deduced from the characteristic magnitude and/or duration of
the fluctuations. Genetically engineered versions of the bacterial pare-for
ming protein alpha-haemolysin have been used to identify and quantify dival
ent metal ions in solution(6). But it is not immediately obvious how versat
ile binding sites for organic ligands might be obtained by engineering of t
he pore structure. Here we show that stochastic sensing of organic molecule
s can be procured from alpha-haemolysin by equipping the channel with an in
ternal, non-covalently bound molecular 'adapter' whim mediates channel bloc
king by the analyte. We use cyclodextrins as the adapters because these fit
comfortably inside the pore and present a hydrophobic cavity suitable for
binding a variety of organic analytes. Moreover, at single sensing element
of this sort can be used to analyse a mixture of organic molecules with dif
ferent binding characteristics. We envisage the use of other adapters, so t
hat the pore could be 'programmed' for a rang of sensing functions.