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

这项小企业创新研究（SBIR）第一阶段项目的更广泛影响/商业潜力是开发一种新型显微镜，该显微镜将生物动力成像与传统的相衬显微镜相结合，用于药物开发和其他研究应用。准确捕获三维（3D）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测量方法——这是药物开发过程的两个关键方面，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。该工具将提取功能信息在更大的组织深度比传统显微镜通过使用细胞运动在活组织内。这种运动是通过反射光检测到的，反射光携带着关于药物在3D组织内作用的重要信息，允许在异质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。该SBIR项目旨在开发和测试一种生物动力显微镜，该显微镜提供了一种新的研究工具，能够从三维组织培养和肿瘤活检中提取高信息量。项目目标是构建一种基于细胞运动检测的新型显微镜，并将显微镜与客户易于使用的软件平台集成。待开发的软件模块驱动用户界面并提供数据可视化。与传统显微镜相比，生物动力显微镜通过对活组织内细胞内运动反射的光使用多普勒标签，在更大的组织深度提取功能信息。这些多普勒标签携带有关药物在3D组织内作用的表型分析信息，这是在个性化癌症治疗中实现肿瘤功能表征的关键一步。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I 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 (3D) 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 project aims to develop and test a bio-dynamic microscope that provides a new research tool capable of extracting high information content from three-dimensional tissue cultures and tumor biopsies. 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. The software modules to be developed drive the user interface and provide data visualization. The bio-dynamic microscope extracts functional information at greater tissue depths than conventional microscopes by using Doppler tags on light reflected from intracellular motions inside living tissue. These Doppler tags carry phenotypic profiling information about the action of drugs inside 3D tissue, a critical step towards functional characterization of tumors as targets in personalized cancer therapy.