Separation of model mixtures of epsilon-globin positive fetal nucleated red blood cells and anucleate erythrocytes using a microfluidic device.

Microfluidic devices are capable of separating microparticles and cells. We developed and tested the efficiency of silicon cross-flow microfilters for the separation of primitive fetal nucleated red blood cells (FNRBCs) and adult anucleate red blood cell (AARBCs) from model mixtures. Stepwise improvements over three generations of device design resulted in an increasing trend in the recovery of FNRBCs. We obtained a recovery of FNRBCs (74.0+/-6.3%, p<0.05, n=5) using the third generation device, with a depletion of 46.5+/-3.2% AARBCs from the cell mixture. The purity of FNRBCs in the enriched fraction was enhanced by a factor of 1.7-fold.

[1]  W. Holzgreve,et al.  An examination of different Percoll density gradients and magnetic activated cell sorting (MACS) for the enrichment of fetal erythroblasts from maternal blood , 2000, Archives of Gynecology and Obstetrics.

[2]  V. Vandelinder,et al.  Separation of plasma from whole human blood in a continuous cross-flow in a molded microfluidic device. , 2006, Analytical chemistry.

[3]  Larry J Kricka,et al.  Micropillar array chip for integrated white blood cell isolation and PCR. , 2005, Biomolecular engineering.

[4]  M. Yamada,et al.  Hydrodynamic filtration for on-chip particle concentration and classification utilizing microfluidics. , 2005, Lab on a chip.

[5]  J. Sturm,et al.  Deterministic hydrodynamics: Taking blood apart , 2006, Proceedings of the National Academy of Sciences.

[6]  Clinical application of microfluidic leukocyte enrichment protocol in mild phenotype sickle cell disease (SCD) , 2009, Biomedical microdevices.

[7]  K. Klinger,et al.  Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY I data , 2002, Prenatal diagnosis.

[8]  Mann A. Shoffner,et al.  Integrated cell isolation and polymerase chain reaction analysis using silicon microfilter chambers. , 1998, Analytical biochemistry.

[9]  M. von Lindern,et al.  The use of in vitro expanded erythroid cells in a model system for the isolation of fetal cells from maternal blood , 1999, Prenatal diagnosis.

[10]  C Hollmann,et al.  DETECTION OF DISSEMINATED TUMOR CELLS IN PERIPHERAL BLOOD , 2005, Critical reviews in clinical laboratory sciences.

[11]  D. Bianchi,et al.  DEVELOPMENT OF A MODEL SYSTEM TO COMPARE CELL SEPARATION METHODS FOR THE ISOLATION OF FETAL CELLS FROM MATERNAL BLOOD , 1996, Prenatal diagnosis.

[12]  L. Voullaire,et al.  Fetal nucleated red blood cells from CVS washings: an aid to development of first trimester non‐invasive prenatal diagnosis , 2001, Prenatal diagnosis.

[13]  M. Rauff,et al.  In vivo model to determine fetal‐cell enrichment efficiency of novel noninvasive prenatal diagnosis methods , 2008, Prenatal diagnosis.

[14]  Nicole Pamme,et al.  Continuous flow separations in microfluidic devices. , 2007, Lab on a chip.

[15]  Chiara Lapucci,et al.  Enrichment of Fetal Nucleated Red Blood Cells from the Maternal Circulation for Prenatal Diagnosis: Experiences with Triple Density Gradient and MACS Based on More than 600 Cases , 1998, Fetal Diagnosis and Therapy.

[16]  H. Ji,et al.  Silicon-based microfilters for whole blood cell separation , 2008, Biomedical microdevices.

[17]  Roberto Guerrieri,et al.  Separation of white blood cells from erythrocytes on a dielectrophoresis (DEP) based 'Lab-on-a-chip' device. , 2005, International journal of molecular medicine.

[18]  Mehmet Toner,et al.  Blood-on-a-chip. , 2005, Annual review of biomedical engineering.

[19]  James N Turner,et al.  Biochip for separating fetal cells from maternal circulation. , 2007, Journal of chromatography. A.

[20]  R. Tompkins,et al.  A microfluidics approach for the isolation of nucleated red blood cells (NRBCs) from the peripheral blood of pregnant women , 2008, Prenatal diagnosis.

[21]  M. Yamada,et al.  Continuous particle separation in a microchannel having asymmetrically arranged multiple branches. , 2005, Lab on a chip.

[22]  M. Kersaudy-Kerhoas,et al.  Recent advances in microparticle continuous separation. , 2008, IET nanobiotechnology.

[23]  S. Digumarthy,et al.  Isolation of rare circulating tumour cells in cancer patients by microchip technology , 2007, Nature.

[24]  N. Fisk,et al.  Characterization of first trimester fetal erythroblasts for non-invasive prenatal diagnosis. , 2003, Molecular human reproduction.

[25]  G. Walker,et al.  Microfluidic aqueous two phase system for leukocyte concentration from whole blood , 2009, Biomedical microdevices.

[26]  M. W. Vaughn,et al.  Microfluidic-based diagnostics for cervical cancer cells. , 2006, Biosensors & bioelectronics.