Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Lab Chip. 2018 Sep 11;18(18):2749-2756. doi: 10.1039/c8lc00650d.
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.
胎儿非整倍体和其他染色体异常影响 1000 例活产中的 9 例。与高流产风险的侵袭性诊断不同，来自母体血液的非侵入性产前诊断 (NIPD) 采样成为胎儿基因筛查的一种有前途的方法。然而，由于母体血液中存在的胎儿细胞数量较少，基于胎儿细胞的 NIPD 具有重大挑战。我们设计了一种频率增强的转铁蛋白受体抗体标记微流控芯片 (FETAL-Chip)，用于从母体血液中有效富集和鉴定循环胎儿细胞，即循环有核红细胞 (cNRBC)。FETAL-Chip 可以显著增强胎儿细胞与抗体包被的微柱之间的相互作用，从而提高捕获效率，同时最小化非特异性吸附。借助免疫染色，我们可以从仅 2 毫升的母体血液中识别出 cNRBC。早在受孕后 7 周并贯穿整个妊娠期间，从志愿者中检测到各种数量的 cNRBC。还进行了基因分析以确认捕获细胞的胎儿来源。通过对 cNRBC 进行简单、非侵入性和高效的富集，本研究提出的方法为非侵入性产前诊断提供了巨大的潜力。
