Results are reported from a combined optical force and electrokinetic microfluidic device that separates individual particulates from molecular components in a mixed sample stream. A pico-Newton optical force was applied to an orthogonal electroosmotic flow carrying a hydrodynamically pinched, mixed sample, resulting in the separation of the various particles from the sample stream. Different combinations of polystyrene, PMMA, and silica particles with a commercially available dye were utilized to test the different separation modes available, from purely optical force to combined optical and electrophoretic forces. The impact of various particle properties on particle separation and separation efficiency were explored, including size (2, 6, 10 μm), refractive index, and electrophoretic mobility. Particle addressability was achieved by moving particles to different outlets on the basis of particle size, refractive index, and electrophoretic differences. Separations of 6 and 10 μm polystyrene particles led to only 3% particle contamination in the original sample stream and interparticle type enrichment levels >80%. The unique addressability of three different particle materials (polystyrene, PMMA, and silica) of the same size (2 μm) led to each being separated into a unique outlet without measurable contamination of the other particle types using optical force and electrophoretic mobility. In addition to particle separation, the device was able to minimize dye diffusion, leading to>95% dye recovery. This combined platform would have applications for noninvasive sample preparation of mixed molecular/particulate systems for mating with traditional analytics as well as efficient removal of harmful, degrading components from complex mixtures.