基于单层MoS2的新型电化学阻抗显微平台用于纤维化过程中单细胞成像研究

纤维化不仅伴随着细胞形态、迁移以及分化的异常，其过度进展还可能引起组织功能的丧失甚至死亡。目前，对纤维化过程中单细胞水平的成像研究还比较有限。本项目拟利用二维纳米材料单层二硫化钼（MoS2）构建一种操作简便、高灵敏、并具有较高时空分辨的新型电化学阻抗显微平台用于单细胞成像分析。与传统获取阻抗的方法不同，本项目通过对光学图像序列依次进行快速傅里叶变换及光电信号转换得到局域阻抗信息，避免了微电极阵列的使用，并提高了成像的信噪比；同时，单层MoS2光学信号对电荷的超灵敏响应进一步提高了方法的灵敏度。利用构建的阻抗显微平台拟开展如下两方面工作：①对纤维化过程中单细胞水平的变化进行实时研究，揭示其空间结构及功能的异质信息；②建立一种纤维化速率的半定量测定方法用于抗纤维化研究。本项目有望加深研究者对纤维化过程中多细胞相互作用的理解，并对相关疾病的诊疗以及抗纤维化药物的研发具有一定的指导意义。

Fibrosis is not only accompanied by dysregulation of cell morphology, migration and cell differentiation, its excessive progress may cause loss of tissue function and even death. At present, the study of single-cell imaging during fibrosis is still limited. This project intends to develop a relatively simple and highly sensitive novel electrochemical impedance microscopy platform with certain spatiotemporal resolution for single-cell imaging analysis, which based on two-dimensional nanomaterial monolayer molybdenum disulfide (MoS2). Different from the traditional impedance measurement, the local impedance information here is obtained by successively performing fast Fourier transform and photoelectric conversion of the optical image sequence. It avoids the use of microelectrode array, thus improves the signal-to-noise ratio of imaging. In addition, the ultra-sensitive response of monolayer MoS2 optical signal to charge further enhances the sensitivity of the method. With the developed impedance platform, we intend to carry out the following two works. ① Real-time study of the changes on single cell level during fibrosis, and revealing its spatial structural and functional heterogeneity. ② Establishing a semi-quantitative method for the fibrosis rate determination for anti-fibrosis study. The project can deepen our understanding of the complex multi-cell interaction during fibrosis, which provides a guidance for the diagnosis and treatment of related diseases as well as the research and development of anti-fibrosis drugs.