The Pacific Northwest National Laboratory (PNNL) is developing an unattended safeguards instrument concept, combining continuous aerosol particulate collection with uranium isotope assay, to provide timely analysis of enrichment levels within low enriched uranium (LEU) facilities. This approach is based on laser vaporization of aerosol particulate samples, followed by wavelength tuned laser diode spectroscopy, to characterize the uranium isotopic ratio by subtle differences in atomic absorption wavelengths. Environmental sampling media from an integrated aerosol collector is automatically introduced into a small, reduced pressure chamber, where a focused pulsed laser vaporizes a 10 to 20-µm sample diameter. The ejected plasma forms a plume of atomic vapor. Tunable diode lasers are directed through the plume and each isotope is detected by monitoring absorbance signals on a shot-to-shot basis. The media is translated by a micron resolution scanning system to fully characterize the sample surface. Single-shot detection sensitivity approaching the femtogram range and relative isotope ratio uncertainty better than 10% has been demonstrated with surrogate materials. In this paper we present measurement results on samples containing background materials (e.g., dust, minerals, soils) laced with micron-sized target particles having isotopic ratios ranging from 1 to 50%.