如何从单细胞水平多参数获取肿瘤细胞电化学特性与图像信息是目前细胞电化学传感领域亟待解决的一个难题。我们拟在前期工作基础上，将高分辨、高灵敏光寻址电位传感器和扫描光诱导阻抗显微成像技术联用，结合微流控芯片，构建无损免标记多通道集成单细胞成像与传感平台；以人乳腺癌细胞为模型，对不同亚型细胞进行光电流检测和成像，使用点接触细胞-芯片耦合模型分析单细胞阻抗和表面电位信息，从单细胞水平评估细胞的电化学异质性；实时在线监测单个乳腺癌MCF-7细胞在不同浓度抗癌药物及其组合作用下电化学响应信号及图像信息的变化，研究药物诱导细胞凋亡动力学过程和非均向特性，揭示肿瘤单细胞电化学特性与药物诱导细胞凋亡过程的重要联系。本项目开发的细胞电化学成像技术能从单细胞水平综合检测与分析肿瘤细胞的异质性及细胞凋亡的动态过程，为细胞病理生理基础研究提供新的技术手段，对肿瘤精准诊断、个性化治疗和指导用药等领域具有重要意义。

Physiological activities of cells are usually coupled with electron and/or electroactive species transferring. It has been shown that cancer cell biological behaviors, including cell adhesion, spreading, proliferation and apoptosis, are always companioned with the alterations in electrochemical properties such as cell surface charge and impedance. Therefore, the development of label-free and non-invasive biosensors for cell electrochemical sensing is particularly important in cancer cell research. Conventional electrochemical methods lake spatial information, making it impossible to investigate cellular heterogeneities, which is of particular importance in cancer precise diagnosis and prognosis. Light-addressable potentiometric sensor (LAPS)/scanning photo-induced impedance microscopy (SPIM) overcomes these problems. Based on an electrolyte-insulator-silicon (EIS) field-effect structure, multi-sites on LAPS/SPIM chips can be addressed by scanning a focused light beam across the sensor substrates, providing information of surface potentials and impedance with lateral resolution. In this project, small peptides of cyclic-Arg-Gly-Asp (RGD)fK modified and self-assembled monolayers (SAMs) insulated LAPS/SPIM combined with microfluidics will be used to consolidate functions of single cell analysis and two-dimensional imaging of electrochemical properties together. To specific, by using the integrated cell-based biosensor, the changes of the local surface charge and impedance due to the attachment of the target cell can be observed by measuring local photocurrents. The cell heterogeneous properties at single cell level of breast cancer cells will be analyzed via high-resolution LAPS/SPIM imaging. Furthermore, as cell death results in dramatic electrochemical property changes, cell apoptosis processes induced by typical anti-cancer drugs such as tamoxifen will be recorded using LAPS/SPIM. The correlation between electrochemical properties of single cells and their drug-induced cell apoptosis processes will be investigated and determined. The proposed technique has the advantages that capable of high-resolution imaging and real-time single cell sensing with muti-channels and multi-parameters, which are not accessible to other electrochemical techniques. The results of this project will provide a novel method for the study of cancer physiopathology basis and impact in the fields of drug screening, drug efficacy evaluation, cancer precise diagnosis as well as personalized treatments.