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A novel kind of multi-core magnetic composite particles,the surfaces of which were respectively modified with goat-anti-mouse IgG and antitransferrin receptor(anti-CD71 ),was prepared.The fetal nucleated red blood cells(FNRBCs) in the peripheral blood of a gravida were rapidly and effectively enriched and separated by the modified multi-core magnetic composite particles in an external magnetic field.The obtained FNRBCs were used for the identification of the fetal sex by means of fluorescence in situ hybridization(FISH) technique.The results demonstrate that the multi-core magnetic composite particles meet the requirements for the enrichment and speration of FNRBCs with a low concentration and the accuracy of detetion for the diagnosis of fetal sex reached to 95%.Moreover,the obtained FNRBCs were applied to the non-invasive diagnosis of Down syndrome and chromosome 3p21 was detected.The above facts indicate that the novel multi-core magnetic composite particles-based method is simple,reliable and cost-effective and has opened up vast vistas for the potential application in clinic non-invasive prenatal diagnosis.