Enhanced isolation and release of fetal nucleated red blood cells using multifunctional nanoparticle-based microfluidic device for non-invasive prenatal diagnostics

Fetal nucleated red blood cells (fNRBC) in maternal peripheral blood has the potential for non-invasive prenatal diagnostics (NIPD), given its intrinsic nature carrying total genetic information of the fetus. Unfortunately, the scarcity of fNRBCs in maternal blood circulation greatly hinders the effective isolation of fNRBCs and its further uses for clinical prenatal diagnostics. Herein, we developed a gelatin nanoparticles (GNPs) decorated microchip that modified with anti-CD147 as specific capture antibody to efficiently isolate fNRBCs from maternal peripheral blood. The corrugated GNP nanocoating on the walls of the channel, together with herringbone grooves in the continuous curved channel design, produced enhanced interactions between fNRBC and the device for better cell capture performance. Furthermore, the captured cells could be gently released for subsequent off-chip analyses, using an enzymatic treatment to dissolve the biodegradable GNP nanocoating. Significant target cell capture efficiency (> 80%), release efficiency (similar to 89%) and purity (similar to 85%) as well as a high viability of > 90% were achieved using simulated spiked samples. fNRBCs were detected from a series of maternal peripheral blood samples ranging from 7 to 13 weeks of gestation, and the diagnostic application for fetal chromosomal disorders was demonstrated. Our strategy may provide new insights into developing an approach to recover fNRBCs from early pregnancy for improved cell-based NIPD.