基于介电泳的多参数流式细胞力学检测技术与应用研究

This project aims to improve the throughput and automatic level of detection of cell mechanics by means of the dielectrophoresis and cytometric micro-chip-based technique. A multi-field coupling model, which integrates the contribution of electrical filed, flow field and cell deformation, will firstly be developed to assess mechanical properties of single cells. Subsequently, a multi-dimensional detection technique will be presented to enhance the specificity and sensitivity of mechanical characterization by comprehensively evaluating the information on electrical impedance, mechanical parameters, and geometrical parameters of cells involved. The proposed detection technique will also be validated by inspecting the inherent correlation between the multi-field parameters and the experimental results of molecular biology based on the cell lines of cervical carcinoma. Finally, the clinical effectiveness and detection reliability will be further confirmed by large clinical sample analysis. In this way, the presented technique based upon dielectrophoresis and cytometric micro-chips is capable of realizing a high throughput, multi-parametric detection for mechanical aspects of single cells in vitro, which is crucial to developing some more efficient and reliable methods for early detection and diagnosis of tumors.

本项目将介电泳技术与流式细胞芯片相结合，提高细胞力学检测的通量和操作的自动化程度；建立电场-流场-细胞变形场的耦合分析模型，提取细胞内在准确的力学性质；将细胞电阻抗信息、力学以及几何参数信息相结合，实现多维多参数表征，进一步提高检测的特异性及效果；以宫颈癌细胞系及临床样本为例，开展大样本量的对照实验，实现基于介电泳的高通量、多参数细胞力学性能检测的新技术、新方法，为肿瘤等疾病的快速准确诊断提供方法学探索。

实现了基于介电泳的高通量细胞力学芯片检测方法；建立了电场-流场-细胞变形场的耦合分析模型，准确提取了细胞内在的力学性质；将细胞电学信息和力学(几何)参数相结合，初步实现了多维多参数表征，提高了细胞检测的特异性及灵敏度；以肿瘤细胞系为例，开展了大样本量的对照实验，初步实现了基于介电泳的高通量、多参数细胞力学性能检测；实验结果发现肿瘤细胞的粘弹性力学性质是受细胞周期调控；发现肿瘤细胞耐药性质与其力学特性存在相关性；发现肿瘤细胞在电信号或刚度梯度信号诱导下能够分别表现出非线性的趋电性和趋硬性响应，且细胞的趋电性和趋硬性行为能够被相对独立的控制；发现乳腺癌细胞可以响应倒U型刚度梯度并触发细胞定向迁移，并且细胞倾向于垂直于刚度梯度方向运动；项目研究成果为肿瘤等疾病的精准诊断、药物筛选等医学应用提供了新方法、新工具。