Instruments for molecular detection at the nano-molar to femto-molar concentration level include a longitudinal capillary column (10) of known wall thickness and diameter. The column (10) contains a medium (24) including a target molecule (30) and a plurality of optically interactive dielectric beads (26) on the order of about 10.sup.-6 meters up to about 10.sup.-3 meters and/or metal nanoparticles (31) on the order of 1-500 nm. A flow inducer (34) causes longitudinal movement of the target molecule within the column (10). A laser (14) introduces energy laterally with respect to the column (10) at a wavelength and in a direction selected to have a resonant mode within the capillary column wall (12) and couple to the medium (24). A detector (40) is positioned to detect Raman scattering occurring along the column (10) due to the presence of the target molecule.