基于正交幅值调制的SICM高分辨率高保真实时动态成像方法研究

The dynamic observation of the surface morphology and fine structure of living cells plays an important role in the study of the physiological characteristics of cells, which can provide significant reference for the early detection of disease and the drug screening. Scanning ion conductance microscopy (SICM) has always been an important research aspect in cell observation, because it can be used to observe the living cells on nano scale in the liquid environment without damage. But the current scanning imaging method for SICM can not satisfy the system demand of high anti-interference, high resolution and fast imaging, meanwhile, because of the limitation of tubular structure on the probe tip of glass tube, the imaging of the ultramicro characteristic structure will be distorted in details. Therefore, this project proposes a new imaging method using orthogonal amplitude modulation scanning, by analysis the mechanism of AC signal orthogonal amplitude component as the feedback control. Based on the optimization method of feedback signal of reverse current compensation and the study of adaptive control algorithm based on prior knowledge, this project will achieve high resolution, high anti-interference, and dynamic fast imaging. At the same time, study on image reconstruction method for ultramicro characteristic structure to realize high fidelity imaging for ultrastructure. The research of this project can provide a new theoretical method and technical means for the observation of living cells on nano scale, and it is of great significance for technical development of single-cell analysis.

活体细胞表面形态及精细结构的动态变化观测对于细胞生理特性研究具有重要作用，能够为疾病早期检测、药物筛选提供重要参考依据。扫描离子电导显微镜（SICM）因其可在液态环境下对活体细胞实现无损伤纳米观测，一直是细胞观测领域的一个重要研究方向。但目前SICM的扫描成像方法无法同时满足系统对高抗干扰性、高分辨率和快速成像三方面的需求，并且，由于玻璃管探针针尖管状结构限制，对超微特征结构进行成像时会造成图像细节失真。因此，本项目提出全新的正交幅值调制扫描成像方法，通过开展交流信号正交幅值分量作为反馈控制量的机理分析，基于逆向电流补偿的反馈信号优化方法和基于先验知识的自适应控制方法研究，实现SICM高分辨率、高抗干扰性、动态快速观测成像；同时开展超微特征结构图像重构方法研究，实现超微结构高保真成像。本项目的研究能够为活体细胞纳米观测提供新的理论方法和技术手段，对单细胞分析技术的发展具有重要意义。

活体细胞表面形态及精细结构的动态变化观测对于细胞生理特性研究具有重要作用，扫描离子电导显微镜子（SICM）因其无损伤纳米观测的特性，成为应用于细胞精细观测的一个重要研究方向。针对这种观测技术对高抗干扰性、高分辨率和快速成像三方面的需求，提出了基于正交幅值调制模式的扫描成像方法，提升了SICM系统看干扰性，并在此基础上，研究了一种基于逆向电流补偿的反馈控制信号优化方法，实现了SICM系统高分辨率扫描成像，研究了一种基于先验知识的自适应控制方法，实现了SICM系统高速扫描成像。完成了探针虚拟形貌还原方法的理论基础研究，为重构高保真表面形貌奠定了坚实的基础。通过本项目的研究为活体细胞纳米观测提供了新的理论方法和技术手段，对单细胞分析技术的发展具有重要意义。