On-column refractive index detector for flash chromatography

A universal detector for on-column analysis in flash chromatography is reported. The detection scheme takes advantage of refractive index changes as analytes move through an illuminated region of the column. The column packing material is a diffuse scattering medium when the refractive index of the solvent is significantly different than that of the packing material. The magnitude of the ‘signal’ depends on the degree to which the refractive index mismatch is changed. An empirical model that qualitatively accounts for the observed trends is presented. This detection scheme provides a simple, inexpensive means to monitor the end of a flash chromatography column in order to determine the exit time of the species of interest, thus greatly reducing the post-column analysis time. Additionally, the detector is movable along the length of the column, offering the potential to monitor separations as they occur.