Polarization microscopy for three-dimensional imaging of biological microstructur

介绍了一种无需标记或染色即可对生物组织成像的新技术，称为Mueller矩阵偏振显微镜，用于可视化各向异性复折射率的分布，各向异性复折射率是内部细胞和组织微结构的固有特性。除了线性双折射(目前在显微镜下研究的唯一偏振特性)，生物组织(细胞)还表现出圆双折射(手性介质中的光学活性)和线性和圆二向色性(正交偏振的差分吸收)，这可能只能从完整的Mueller矩阵中识别出来。这些性质的精确测量将为了解复杂生物实体的结构组织打开一扇新的窗口。这些新能力将提供对发育和结构生物学研究的细胞和活组织的微观结构、它们的转化和相互作用的基本见解，从而改善癌症和退行性疾病的诊断、预后和治疗。物理科学公司(PSI)在哈佛大学和系统生物学中心的咨询下，马萨诸塞州总医院将开发一种简单但通用且坚固耐用的偏振显微镜，用于反射和透射式三维全米勒矩阵成像，并将该仪器用于天然和合成组织研究。偏振分析是基于四个液晶可变延迟器的配置设计的，没有移动部件。米勒旋光仪与立体成像相结合，用于样品的三维重建。在这项研究中开发的技术将成为一种有价值的工具，在生物医学成像方面具有巨大的潜力，特别是在成像和监测细胞微结构及其转化方面。这样的装置可能形成一种新的检测方法的基础，商业应用于斑马鱼或用于药物发现的其他小动物的高通量成像。公共卫生相关性：项目简介本研究的目的是开发一种简单但通用且坚固耐用的偏振显微镜，用于三维偏振成像，并将该仪器用于生物组织分析。这一新型仪器将允许对生物组织结构特性的无标记、深入探索，从而改进癌症和退行性疾病的诊断和治疗。

DESCRIPTION (provided by applicant): Project Summary/Abstract A novel technique for imaging biological tissue without labeling or staining, called Mueller matrix polarization microscopy, is introduced for visualizing the distribution of the anisotropic complex refractive index, an intrinsic property of the internal cellular and tissue microstructures. In addition to linear birefringence (the only polarization property currently investigated in microscopy) biological tissue (cells) exhibits also circular birefringence (optical activity in chiral media) and linear and circular dichroism (differential absorption for orthogonal polarizations) that can potentially be identified only from a complete Mueller matrix. Precise measurement of these properties will open a new window into the structural organization of complex biological entities. The new capabilities will provide fundamental insight into the microstructure of cells and living tissue, their transformations and interactions, studied in developmental and structural biology, leading to improved diagnosis, prognosis, and treatment of cancer and degenerative diseases. Physical Sciences Inc. (PSI) with consultation from Harvard University and the Center for System Biology, Massachusetts General Hospital will develop a simple yet versatile and robust polarization microscope for both reflection and transmission three-dimensional full Mueller matrix imaging, and to use this instrument for natural and synthetic tissue research. The polarization analysis is based on four liquid crystal variable retarders in a configuration designed without moving parts. The Mueller polarimeter is combined with stereoscopic imaging for three-dimensional reconstruction of the sample. The technology developed during this research will become a valuable tool with tremendous potential for biomedical imaging in general, and for imaging and monitoring cellular microstructures and their transformations in particular. Such a device may form the basis of a new assay with commercial applications to high- throughput imaging of zebrafish or other small animals used in drug discovery. PUBLIC HEALTH RELEVANCE: Project Narrative The purpose of this research is to develop a simple yet versatile and robust polarization microscope for three-dimensional polarization imaging, and to use this instrument for biological tissue analysis. This novel instrumentation will allow label-free, in-depth exploration of biological tissue structural properties leading to improved diagnosis and treatment of cancer and degenerative diseases.