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The use of fetal cells enriched from maternal peripheral blood for genetic analysis would be a significant advancement for prenatal diagnosis. For over two decades, researchers have employed different techniques (including density gradients, red blood cell lysis, fluorescence-activated cell sorter and magnetic cell separation) to enrich fetal cells that exist in low levels in maternal blood. Despite extensive attempts by various groups and companies, reliable isolation of a sufficient amount of fetal nucleated cells remains a monumental challenge. AVIVA Biosciences Corp. has been developing a technology that allows significant enrichment and recovery of rare fetal cells from maternal peripheral blood. This review will characterize fetal cell types present in maternal blood, technologies used to enrich for these cells and the issues involved with rare fetal cell separation.