Described herein are methods, devices, and compositions for fractionation and processing of microparticles from biological samples, and to methods for obtaining and using the microparticles for biomarker discovery. Biological samples include cell-free fluids, for example blood plasma, blood serum, cerebrospinal fluid, urine, and saliva, as well as conditioned media. Conditioned media is the liquid growth media used to propagate cells in vitro. Purification of microparticles from cell-free fluids is challenging, typically accomplished by prolonged ultracentrifugation. Described herein is an alternative method for efficiently harvesting and processing microparticles from cell-free fluids and from conditioned media. Embodiments described herein relate to use of the microparticles and their contents recovered from conditioned media derived from propagation of human and animal cells, as a source of biomarkers for diagnosis and prognosis of diseases and pathological conditions.