Enhanced Isolation of Fetal Nucleated Red Blood Cells by Enythrocyte-Leukocyte Hybrid Membrane-Coated Magnetic Nanoparticles for Noninvasive Pregnant Diagnostics

Abstract

Fetal nucleated red blood cells (fNRBCs) in maternal peripheral blood containing the whole genetic information of the fetus may serve for noninvasive pregnant diagnostics (NIPD). However, the fetal cell-based NIPD is seriously limited by the poor purity of the isolated fNRBCs. Recently, the biomimetic cell membrane-camouflaged nanoparticles containing outstanding features have been widely used to detect and isolate rare cells from the peripheral blood samples. In this work, enythrocyte (RBC) and leukocyte (WBC) membranes are fused and coated onto magnet nanoparticles and then modified with anti-CD147 to isolate fNRBCs from the maternal peripheral blood with significant efficiency (∼90%) and purity (∼87%) in simulated spiked blood samples. Further, fNRBCs were isolated and identified from a series of maternal peripheral blood samples coming from pregnant women of 11–13 gestational weeks, and different chromosomal aneuploidies were diagnosed using fNRBCs isolated from maternal blood in early pregnancy. Our strategy may offer additional opportunity to overcome the limitations of current cell-based NIPD platforms.

Hybrid Membrane-Coated Biomimetic Nanoparticles (HM@BNPs): A Multifunctional Nanomaterial for Biomedical Applications

“…For instance, the recognition and active interactions between platelets and CTCs which have been proven to critically contribute to tumor metastasis, , may help to some extent isolate CTCs from peripheral blood. Leukocyte membranes have been employed to isolate rare cells by avoiding interactions with background WBCs …”

“…(g) Capture efficiency of various NPs on the impact of incubation time. Reprinted with permission from ref . Copyright 2018 American Chemical Society.…”

A light-induced hydrogel responsive platform to capture and selectively isolate single circulating tumor cells

“…Therefore, various platforms for separating CTCs have been developed in recent years. Currently, the main principles of isolating CTCs are based on the cells’ physical properties, 10 immunochemical properties, 11 microfluidic technology, 12 and other factors. 13–15 However, current approaches inevitably also isolate untargeted cells due to the nonspecific adsorption.…”

Detection of nucleated red blood cells using the Mindray BC-6800Plus hematology analyzer: a clinical performance evaluation

“…Combined with a patient's clinical symptoms and history, routine peripheral blood examinations play a vital role in the clinical diagnosis and treatment of many diseases, especially diseases involving the blood system (1). For example, hemoglobin (HGB) levels and platelet (PLT) counts can determine whether a patient needs blood transfusions, the number of white blood cells (WBCs) can indicate the degree of infection, and the appearance of abnormal cells may be closely related to diseases of the circulatory system and tumors (2)(3)(4). Furthermore, the presence of nucleated red blood cells (NRBCs) is closely associated with many serious diseases.…”