SBIR Phase II: Development of a Microscope to Detect Cellular Motion in Three-dimensional Tissue

小型企业创新研究(SBIR)第二阶段项目的更广泛影响/商业潜力是开发一种将生物动态成像与传统相差显微镜相结合的新型显微镜，用于药物开发和其他研究应用。准确捕捉三维生物系统的特征提供了更现实的药物疗效和反应异质性的衡量标准，这是药物开发过程中的两个关键方面，有助于找到正确的药物剂量和组合，以最小的毒副作用杀死癌细胞。这一工具将利用活组织内的细胞运动，在比传统显微镜更深的组织中提取功能信息。这种运动由反射光检测，反射光携带有关药物在3D组织中的作用的重要信息，允许在不同的三维组织系统中进行药物评估，并为药物开发提供新的见解。这个SBIR第二阶段项目提供了一种能够从三维活体组织培养和肿瘤活检中提取高内容信息的工具。它通过在活组织内细胞内运动散射的光上使用多普勒标签，在比传统显微镜更深的组织深度提取这种功能信息。这些新颖的多普勒标签携带有关药物在3D组织内作用的表型特征信息，允许在异质三维组织中进行药物评估，并为药物开发和治疗提供新的见解。该项目的目标是构建一种基于细胞运动检测的新型显微镜，并将该显微镜与客户易于使用的软件平台集成在一起。在第二阶段完成后，一种商业生物动力学显微镜产品将准备好向生命科学客户转售领先的显微镜。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is to develop a new microscope that integrates biodynamic imaging with conventional phase contrast microscopy for use in drug development and other research applications. Accurately capturing the signatures of three-dimensional biological systems provides more realistic measures of drug efficacy and response heterogeneity - two critical aspects of the drug-development process that help find the right drug doses and combinations to kill cancer cells with minimal toxic side effects. This tool will extract functional information at greater tissue depths than conventional microscopies by using cellular motions inside living tissue. The motion is detected by reflected light that carries with it important information about the action of drugs inside 3D tissue, allowing drug evaluations in heterogeneous three-dimensional tissues systems, and providing new insights for pharmaceutical development. This SBIR Phase II project provides a tool capable of extracting high-content information from inside three-dimensional living tissue culture and tumor biopsies. It extracts this functional information at greater tissue depths than conventional microscopies by using Doppler tags on light scattered from intracellular motions inside living tissue. These novel Doppler tags carry phenotypic profiling information about the action of drugs inside 3D tissue, allowing drug evaluations in heterogeneous three-dimensional tissues and providing new insights for pharmaceutical development and therapeutics. The project goals are to construct a new type of microscope based on the detection of cellular motions, and to integrate the microscope with a software platform that is easy to use by customers. Upon completion of this Phase II, a commercial biodynamic microscope product will be ready for value-added resale of leading microscopes to life sciences customers.