AbstractMultiple myeloma is a cancer of disordered plasma cells. The disease poses significant challenges for clinical management where cytogenetic analysis, such as FISH (fluorescent in situ hybridization), was commonly used for diagnosis and prognosis. Beads based enrichment of plasma cells are widely used to enhance FISH sensitivity and specificity. However conventional beads-based methods often require time-consuming sample preparation and results in low cell recovery.Here we present an easy and automated method to positively isolated CD138+ plasma cells from bone marrow samples. The method is developed on a novel designed magnetic separation system, MARS®. MARS® is matrix-free magnetic separation platform providing high purity, high recovery, and high capacity for cell isolation. Magnetic bead labeled CD138+ cells are isolated directly from bone marrow and peripheral blood without centrifugation. In the pilot study, U266 cells were spiked into peripheral blood from 0.5% to 2.0% of white blood cells frequency range. In addition, healthy donor bone marrow cell sample with 0.04% plasma cells were processed on MARS®. Plasma cells were isolated at 1mL/min flow rate followed by automated rinsing and releasing on MARS®. 48% to 80% recovery of the plasma cells were obtained. Results show our method has advantage in fast (<30 minutes), easy process with high recovery. Our next objective will be to validate the method on Multiple Myeloma patient specimens and compared to conventional beads-based enrichment methods. Enriched plasma cells will be analyzed by FISH to prove the enhanced sensitivity with better enrichment method.