基于石墨烯基光学生物传感器的高特异性显微成像研究

无标记成像技术克服了荧光标记物的干扰，实现以无损、非侵入方式动态观测活细胞内部结构和细胞生理过程，已成为研究活细胞生物过程的重要技术手段。石墨烯基折射率显微成像技术是一种无标记显微成像技术，具有分子水平的灵敏度和亚波长量级空间分辨率，已应用到癌细胞筛选、细胞耐药性检测等领域。针对现有技术存在无法对目标靶分子进行特异性识别的问题，本课题提出了“细胞折射率显微特异性”的科学假说，并进行下列研究：研究细胞内分子结构变化诱导细胞折射率变化的新机制；构建折射率显微结果与荧光显微结果之间的映射关系；利用基于深度学习算法的虚拟染色技术，实现用细胞折射率显微图像对特异性目标分子分布规律的预测，并以荧光显微图像的形式输出。通过上述研究获得无标记、高灵敏度、高特异性、高空间分辨率细胞显微成像技术的理论和实验方法。该技术具有替代现有荧光显微成像技术的潜力，为在分子水平研究细胞生命活动提供重要研究手段。

The label-free imaging technology overcomes the interference of fluorescent markers, and realizes the dynamic observation of the internal structure and cell physiological process of living cells in a non-destructive and non-invasive manner. It has become an important technical means to study the biological processes of living cells. Microimaging technology of Graphene-based cell refractive index is a label-free micro-imaging technology with molecular-level sensitivity and sub-wavelength spatial resolution. It has been applied to cancer cell screening, cell drug resistance detection and other fields. However, this technology has a problem that the target molecule cannot be specifically identified. For this reason, the scientific hypothesis of "microscopic specificity of cell refractive index" is proposed in our research, and the following researches are carried out. Firstly, we need research the new mechanism of changes in the refractive index of the cell caused by the changes in molecular structure of intracellular compounds. Secondly, we need build the mapping relationship between microscopic results of refractive index and microscopic results of fluorescence. At last, we need to use virtual staining technology based on a deep learning algorithm to achieve accurate prediction about distribution law of specific target molecule by using dynamic cell refractive index microscopic images. The above researches will obtain the theoretical and experimental methods of cell microscopic imaging technology with label-free, high sensitivity, high specificity and high spatial resolution. This technology has the potential to replace the existing fluorescence microscopic imaging technology, and provides an important research tool for studying cell life activities at the molecular level.