A laser desorption ion source provides enhanced ion sampling efficiency and measurement sensitivity by using one or more ion guides to effectively capture ions in a plume emitted from the ion target and guide the ions through an aperture into a downstream vacuum chamber. In one configuration using two RF multipole ion guides, a first RF multipole ion guide disposed next to the ion target is selected to be sufficiently large to capture a substantial portion of the plume, while the second RF multipole ion guide disposed between the first multipole ion guide and the aperture has a smaller dimension to assist focusing of ions into the aperture. The first RF multipole ion guides the ions in the plume into the second RF multipole ion guide, which then focuses the ions so that they pass through the aperture into the downstream vacuum chamber.