基于细胞机械/电子特性高通量同时表征的肿瘤细胞检测研究

恶性肿瘤细胞生物化学/物理特性的检测是癌症诊断的一个核心环节，以判断细胞癌变的程度、扩散能力以及在药物作用下的反应。传统的细胞检测方法仅能高通量表征细胞的生物化学特征,而在细胞生物物理特性表征中存在低通量的缺点，不具备采集大样本细胞的生物物理特征的能力。由于与细胞尺寸相比拟，基于微流控芯片的传统压缩通道（Constriction Channel横截面积小于细胞横截面积）可实现单细胞机械电子特性的高通量表征，但仍无法采集独立于细胞尺寸的参数。本项目通过研究压缩通道横截面与细胞填充程度的关系，结合阻抗频谱解决细胞机械电子特性表征中的漏压漏电流问题，建立细胞在压缩通道中的等效机械电子模型，突破细胞机械电子特性参数表征中的细胞尺寸无关化难题，实现独立于细胞尺寸的机械电子特性参数（如杨氏模量和细胞膜比电容）的高通量同时采集，探索其与细胞癌变的关系，为恶性肿瘤的检测和治疗研究提供可靠的方法和途径。

Characterization of tumor cells is one of the key components in cancer diagnosis. Compared to biochemical property evaluations, traditional techniques for single-cell biophysical property testing suffer from the problem of low throughput,limiting their values in cancer cell detection. Due to comparable dimensions to biological cells, Microfluidics based constriction channel design has been demonstrated for high-throughput single-cell electromechanical property characterization, which, however, is not capable of collecting size-independent parameters. In this study, we plan to develop a microfluidic platform by combining the modified constriction channel design with impedance spectroscopy, enabling high-throughput collection of Young's modulus and specific membrane capacitance of tumor cells. In this platform, the effects of the constriction channel cross sections on cell filling status are investigated to deal with the pressure and current leaking issue. Based on proposed equivalent electromechanical models of the constriction channel for cellular measurements, size-dependent electromechanical parameters such as entry time and impedance values are translated into size-independent parameters such as Young's modulus and specific membrane capacitance. In the long term, this platform may demonstrate the concept feasibility of using biomechanical properties of single cells as biomarkers for cancer detection.