Polarization microscopy for three-dimensional imaging of biological microstructur

项目概述/摘要介绍了一种无需标记或染色的生物组织成像新技术，称为穆勒矩阵偏振显微镜，用于可视化各向异性复折射率的分布，这是细胞和组织内部微观结构的固有特性。除了线性双折射（目前在显微镜中研究的唯一偏振特性）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（正交偏振的微分吸收），这可能只能从完整的穆勒矩阵中识别出来。对这些特性的精确测量将为研究复杂生物实体的结构组织打开一扇新的窗口。这些新功能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，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）在哈佛大学和麻省总医院系统生物学中心的咨询下，将开发一种简单而通用且坚固的偏振显微镜，用于反射和透射三维全米勒矩阵成像，并将该仪器用于自然和合成组织研究。极化分析是基于四个液晶可变缓速器在一个没有运动部件的结构中进行的。米勒偏振计与立体成像相结合，用于样品的三维重建。在这项研究中开发的技术将成为具有巨大潜力的有价值的生物医学成像工具，特别是对细胞微结构及其转化的成像和监测。这种装置可构成具有商业应用的新测定的基础，用于药物发现中使用的斑马鱼或其他小动物的高通量成像。本研究的目的是开发一种简单而通用且坚固的偏振显微镜，用于三维偏振成像，并将该仪器用于生物组织分析。这种新型仪器将允许无标签，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.