微纳流体中低浓度ctDNA的快速电动富集与提取力学机制及实验研究

循环肿瘤DNA(ctDNA)是早期肿瘤的有效标记物，如何在其含量极低时进行有效探测，是实现肿瘤早期检测的前提。然而研究难点在于，流体环境中极少量ctDNA的快速富集与提取力学机制、方法均不明确，因此亟需对上述问题开展系统研究。基于微纳流体中的离子浓度极化(ICP)效应和液滴功能，有望实现纳-微界面带电分子的高效电动富集与辅助提取，为后续检测研究奠定基础。为此，本项目将首先探索纯法向电场ICP效应下ctDNA电动纳流体富集力学机制，以降低探测极限浓度；然后，建立跨尺度有限元多相流数理模型，以探索压力脉冲调控富集塞位置的物理本源，并掌握利用微流体液滴提取有效浓度ctDNA的关键实验技术规律；最后，搭建串联电动纳流体ctDNA高倍率富集、受限空间微流控液滴辅助提取以及后续检测等模块的集成化片上诊断平台。预期成果将有利于明晰微纳流体中带电分子的精准操控力学机制，并为肿瘤早期检测研究提供有力支撑。

Circulating tumor DNA (ctDNA) molecule is an efficient biomarker for tumors. How to detect it effectively when the content of ctDNA is extremely low becomes the premise of early detection of tumor disease. However, the research difficulty consists in that the underlying mechanism and method of rapid enrichment and extraction of a small amount of ctDNA in the fluidic environment are still not clear, so it is urgent to carry out systematic research to overcome the above issue. Based on the effect of ion concentration polarization (ICP) and droplet function in micro-nano fluid, it is expected to realize highly-efficient electrokinetic enrichment and auxiliary extraction of charged molecules at the micro-nano interface, which lays a solid foundation for subsequent detection. For such, this project will firstly explore the mechanical mechanism behind electrical nanofluidic preconcentration of ctDNA under pure normal electric field ICP effect, so as to reduce the concentration of detection limit; Then, a cross-scale multiple-phase flow model based on finite element algorithm will be established to explore the physical origin of the regulation of the concentration plug location by pressure pulse, and master the key experimental technique rules of extracting effective ctDNA concentration by microfluidic droplets. Finally, by connecting ICP-enabled high-magnification ctDNA nanofluidic enrichment, microfluidic droplet assisted extraction in confined space, and subsequent detection modules in series, a highly integrated on-chip diagnosis platform will be developed. It is expected that our results will help clarify the mechanical mechanism of precise manipulation of charged molecules in the micro-nano fluid, providing a strong technical support for early detection of tumor disease.