生物折射率三维无标记定量成像研究进展  

Progress of Three-Dimensional,Label-Free Quantitative Imaging of Refractive Index in Biological Samples

作　　者：杨泽文 张璐[1] 吕宁 王慧君 张镇西[2] 袁莉[3] Yang Zewen;Zhang Lu;Lii Ning;Wang Huijun;Zhang Zhenxi;Yuan Li(State Key Laboratory for Manufacturing Systems Engineering,Xi’an Jiaotong University,Xi’an,Shaanxi 710049,China;Key Laboratory of Biomedical Information Eyigiiieering of Ministry of Education,Xi’an Jiaotoug University,Xi’an,Shaanxi 710049,China;Clinical Lab,the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an,Shaanxi 710061,China)

机构地区：[1]西安交通大学机械制造系统工程国家重点实验室,陕西西安710049 [2]西安交通大学生物医学信息工程教育部重点实验室,陕西西安710049 [3]西安交通大学第一附属医院检验科,陕西西安710061

出　　处：《中国激光》2022年第5期83-107,共25页Chinese Journal of Lasers

基　　金：国家自然科学基金(61875160)。

摘　　要：折射率是生物样本最重要的光学属性,经常作为内源性“标记物”进行无标记定量成像。虽然通过测量光程差获取相位信息的传统定量相位成像方法已被广泛研究,然而其获取的相位结果是样本折射率与厚度的耦合产物,无法重建三维形态学信息。近年来,以光学投影层析方法为开端,研究人员率先开启了以三维折射率定量成像为目标的形态学特征重建方法研究。然而光学投影层析方法未考虑衍射效应,导致其精度不足。为解决该问题,基于散射反演求解的光学衍射层析技术应运而生,并在无标记生物三维成像方面展现出巨大的潜力。本文锁定生物折射率三维无标记定量成像研究,聚焦光学投影层析和光学衍射层析两种方法的发展历程,从正向测量模型、反演算法以及实现方法三方面进行综述,并对该研究未来的工作进行展望。Significance Optical microscopic imaging is vital for observing and studying biological cells and tissues. Fluorescent probes and other chemical reagents are commonly used for exogenous labeling of cells in clinical diagnosis and biomedical research because biological samples absorb little visible light, making them colorless and translucent. Although these labeling methods can improve imaging contrast and specificity, phototoxicity destroys samples to some extent and photobleaching affects long-term observation. Furthermore, many subcellular structures, such as lipids, are extremely difficult to label, which limits labeling methods’ applications. Hence, optical imaging methods for label-free samples are considered to be an important research field for simplifying the time-consuming sample preparation process and for reducing biological interference from fluorescent reagents on samples to meet clinical requirements. The interaction of light and samples can become a promising solution using an optical microscopic imaging method to obtain morphological and biological features of label-free samples. Considering light as electromagnetic waves, biological samples can be characterized by their complex refractive index. The quantitative measurement of the refractive index has experienced a long period of development as an endogenous “label” of biological samples, which includes: a) the average refractive index of a cell population suspended in a medium;b) the effective refractive index of a single cell;c) the two-dimensional(2 D) refractive index mapping imaging of a single cell;and d) the three-dimensional(3 D) refractive index distribution imaging of a single cell. Among them, a) and b) are not involved in the imaging process, and only one refractive index value is measured to represent a cell population or a single cell, which can provide very limited information. As a result, researchers are interested in label-free 2 D imaging and 3 D imaging based on a sample’s refractive index. For label-free “thin” b

关 键 词：医用光学 三维显微成像 无标记成像 折射率定量成像 光学投影层析 光学衍射层析 散射反演 

分 类 号：O436[机械工程—光学工程]