Frequency-enhanced transferrin receptor antibody-labelled microfluidic chip (FETAL-Chip) enables efficient enrichment of circulating nucleated red blood cells for non-invasive prenatal diagnosis

Abstract

Fetal aneuploidy and other chromosomal aberrations affect 9 in 1000 live births. Unlike the invasive diagnosis with high risk of miscarriage, non-invasive prenatal diagnosis (NIPD) sampling from maternal blood becomes a promising way for fetal genetic screening. However, fetal cell-based NIPD has a major challenge due to the small number of fetal cells present in maternal blood. We designed a frequency-enhanced transferrin receptor antibody-labelled microfluidic chip (FETAL-Chip) for efficient enrichment and identification of circulating fetal cells, i.e., circulating nucleated red blood cells (cNRBCs) from maternal blood. The FETAL-Chip can dramatically enhance the interaction of fetal cells with antibody-coated microposts to increase the capture efficiency while minimizing nonspecific adsorption. With the help of immunostaining, we can identify cNRBCs from as little as 2 milliliter maternal blood. Various numbers of cNRBCs were detected from volunteers as early as 7 weeks after conception and throughout the entire pregnancy. Gene analysis was also carried out to confirm the fetal origin of captured cells. With easy, non-invasive and highly efficient enrichment of cNRBCs, the method presented here offers great potential for non-invasive prenatal diagnosis.