循环胎儿细胞的多维度富集微流控芯片的构建及在无创产前检测中的应用

Detection of circulating fetal cells (CFC) in the maternal peripheral blood may serve as a prospective testing method competing with the cell-free DNA, in non-invasive prenatal testing (NIPT). However, the low amount of CFC limited the application of CFC-based NIPT. In this project, a multi-dimensional microfluidic device will be constructed for efficient enrichment of CFC. Interfacial viscoelastic separation is first introduced in the deterministic lateral displacement (DLD) arrays to increase the separation efficiency. Most blood cells will be depleted by interfacial viscoelastic channel and then a DLD array will separated the other cells to obtain CFC with high purity. To overcome the size overlay of CFC and blood cells, a selective size amplification method will be used to increase the size of CFC. This physical and label-free CFC separation system opens a new way of fetal cell enrichment. In the end, genetic diseases screening of fetus will be carried out by whole genome sequencing. The successful implementation of this project will effectively promote the application of CFC-based NIPT, laying the foundation for the development of a new generation of prenatal diagnostic techniques.

孕妇外周血中的循环胎儿细胞(CFC)能够无创、全面地反映胎儿的遗传信息，是无创产前筛查及诊断的理想靶标。如何高纯度、高效地分离孕妇外周血中的循环胎儿细胞是其应用于无创产前检测的瓶颈问题。本项目拟利用微尺度粘弹性效应的血细胞高效分离能力，联合确定性侧向位移的高纯度细胞分选性能，构建高通量、易回收、一体化的多维度富集微流控芯片；拟利用微珠免疫识别手段，实现胎儿细胞的选择性尺寸增大，解决胎儿细胞与血细胞尺寸区分度低的难题，实现孕妇外周血中循环胎儿细胞的高纯度富集；开发基于胎儿全基因组的遗传异常分析方法，实现胎儿的遗传疾病筛查。项目的成功实施将有效推进循环胎儿细胞在无创产前筛查中的应用，为新一代产前诊断技术的开发奠定基础。

孕妇外周血中的循环胎儿细胞(CFC)能够无创、全面地反映胎儿的遗传信息，是无创产前筛查及诊断的理想靶标。如何高纯度、高效地分离孕妇外周血中的循环胎儿细胞是其应用于无创产前检测的瓶颈问题。本项目利用微尺度粘弹性效应的血细胞高效分离能力，联合确定性侧向位移的高纯度细胞分选性能，构建高通量、易回收、一体化的多维度富集微流控芯片，实现孕妇外周血中循环胎儿细胞的高纯度富集；开发基于胎儿全基因组的遗传异常分析方法，实现胎儿的遗传疾病筛查。项目的实施将有效推进循环胎儿细胞在无创产前筛查中的应用，为新一代产前诊断技术的开发奠定基础。