Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Department of Laboratory Medicine, The First Affiliated Hospital of Xiamen University, Xiamen Key Laboratory of Genetic Testing, Xiamen, 361005, China.
Anal Chem. 2020 Jul 7;92(13):9281-9286. doi: 10.1021/acs.analchem.0c01622. Epub 2020 Jun 9.
Circulating fetal nucleated cells (CFCs) carrying whole genomic coding of the fetus in maternal blood have been pursued as ideal biomarkers for noninvasive prenatal testing (NIPT). However, a significant limitation is the need to enrich sufficient cells in quantity and purity for fetal genetic disorder diagnosis. This study for the first time demonstrates a stimuli-responsive ligand enabling interface on array patterned microfluidic chip (NIPT-Chip) for high efficient isolation and release of CFCs in untreated whole blood. Deterministic lateral displacement (DLD)-array was patterned in the chip to increase collision frequency between CFCs and surface-anchored antibody to achieve high efficient cell capture. More importantly, the stimuli-responsive interface enables gentle release of captured CFCs through a thiol exchange reaction for downstream gene analysis of NIPT. With the advantages of simple processing, efficient isolation, and gentle release, NIPT-Chip offers great potential for clinical translation of circulating fetal cell-based NIPT.
循环胎儿有核细胞（CFCs）在母体血液中携带胎儿完整的基因组编码，一直被作为非侵入性产前检测（NIPT）的理想生物标志物进行研究。然而，一个显著的局限性是需要富集足够数量和纯度的细胞，以用于胎儿遗传疾病的诊断。本研究首次证明了一种刺激响应性配体，可用于在微流控芯片（NIPT-Chip）上实现高效的界面，用于在未处理的全血中高效分离和释放 CFCs。芯片中设计了确定性侧向位移（DLD）阵列，以增加 CFCs 与表面锚定抗体之间的碰撞频率，从而实现高效的细胞捕获。更重要的是，刺激响应性界面可通过硫醇交换反应实现温和释放捕获的 CFCs，用于 NIPT 的下游基因分析。NIPT-Chip 具有简单处理、高效分离和温和释放的优势，为基于循环胎儿细胞的 NIPT 的临床转化提供了巨大的潜力。
