Confinement and Detection of Single Molecules in Submicrometer Channels

Detection channels with submicrometer dimensions (500−600 nm i.d.) have been produced directly on electrophoresis capillaries for confinement and detection of single molecules at room temperature. These restrictive channels markedly reduce the Brownian motion of low molecular weight analytes and allow detailed studies of single molecules in solution. With a confocal fluorescence microscope, single molecules have been observed for an extended period of ∼60 ms, which is 50−100 times longer than the bulk diffusion time. These molecules have also been manipulated by an electrokinetic force and detected on-line with high signal-to-noise ratios.