THE change in conductance of a small electrolyte-filled capillary owin
g to the passage of sub-micrometre-sized particles has long been used
for particle counting and sizing. A commercial device for such measure
ments, the Coulter counter, is able to detect particles of sizes down
to several tenths of a micrometre(1-3). Nuclepore technology (in which
pores are etched particle tracks) has extended the lower limit of siz
e detection to 60-nm particles by using a capillary of diameter 0.45 m
u m (ref. 4). Here we show that natural channel-forming peptides incor
porated into a bilayer lipid membrane can be used to detect the passag
e of single molecules with gyration radii as small as 5-15 Angstrom. F
rom our experiments with alamethicin pores we infer both the average n
umber and the diffusion coefficients of poly(ethylene glycol) molecule
s in the pore. Our approach provides a means of observing the statisti
cs and mechanics of flexible polymers moving within the confines of pr
ecisely defined single-molecule structures.