Polarization microscopy for three-dimensional imaging of biological microstructur

描述（由申请人提供）：项目摘要/摘要一种用于成像生物组织而无需标记或染色的新技术，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，内部细胞和组织微观结构的固有特性。除了线性双折射（目前显微镜中研究的唯一偏振特性）之外，生物组织（细胞）还表现出圆双折射（手性介质中的光学活性）以及线性和圆二色性（正交偏振的差分吸收），这些都可能只能从完整的穆勒矩阵中识别。对这些特性的精确测量将为复杂生物实体的结构组织打开一扇新的窗口。这些新的能力将为细胞和活组织的微观结构、它们的转化和相互作用提供基本的见解，并在发育和结构生物学中进行研究，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)在与哈佛大学和系统生物学中心的协商下，马萨诸塞州总医院将开发一种简单而多功能且坚固耐用的偏振显微镜，用于反射和透射三维全穆勒矩阵成像，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没有移动部件。Mueller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个有价值的工具，具有巨大的潜力，用于生物医学成像，特别是成像和监测细胞微结构及其转化。这样的装置可以形成一种新的测定方法的基础，该方法具有商业应用，可以对斑马鱼或其他用于药物发现的小动物进行高通量成像。公共卫生相关性：项目叙述本研究的目的是开发一种简单而多功能和强大的三维偏振成像偏振显微镜，并使用该仪器进行生物组织分析。这种新型仪器将允许无标记，深入探索生物组织结构特性，从而改善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.