Microfluidic platform for solid tumor mechanics and invasion

项目摘要 癌症转移占所有癌症死亡的90%以上。转移瘤细胞的重要能力 包括脱离原发肿瘤并侵袭周围组织，然后扩散到 继发性肿瘤部位。肿瘤细胞快速生长和血管异常引起的实体瘤应激 长期以来，组织一直与癌症预后不良有关。尽管临床上很重要，但基本的 对肿瘤机制及其与肿瘤侵袭的关系缺乏了解。这在一定程度上是因为 能够在生理相关的3D环境中定量研究肿瘤力学的体外工具。 流变仪等现有的材料力学测试工具在当前的材料力学测试中发挥了重要的作用 了解生物材料和肿瘤力学。然而，传统的流变仪并不容易制造 与细胞培养条件和结果兼容的空间平均，掩盖了重要的单个细胞和 分子水平信息。原子力显微镜和吸管吸入法是细胞培养相容的，但低 吞吐量。这项研究的目标是开发一种高通量微流变仪，用于 生理真实感3D环境下肿瘤力学和侵袭的系统研究 具有单细胞和椭球体水平的动态光学成像。我们将提出一套原则来治理 肿瘤力学及其与侵袭性的关系。我们假设肿瘤力学是一个关键的预测因子 肿瘤侵袭性。拟议的项目具有创新性，因为它代表了第一代 能够对肿瘤力学研究进行全面机械测试的微流变仪，以及 同时兼容肿瘤侵袭实验。这里开发的工具可以轻松地扩展到 使用其他生活材料，在这里学到的经验教训最终将导致重要的知识 开发癌症的新诊断或/和治疗策略。

Project Summary Cancer metastasis accounts for over 90% of all cancer deaths. Important abilities of metastatic tumor cells include breaking away from the primary tumor and invading into surrounding tissue before disseminating to secondary tumor sites. Solid tumor stress caused by rapid growth of tumor cells and abnormality of the vascular tissue has long been associated with poor prognosis of cancer. Despite the clinical importance, the basic understanding of tumor mechanics and its relation to tumor invasion is lacking. This is in part due to the lack of in vitro tools that are able to investigate quantitatively tumor mechanics in a physiologically relevant 3D setting. Current material mechanical testing tools such as the rheometer have played important roles in our current understanding of biomaterials and tumor mechanics. However, the conventional rheometer is not easily made compatible with cell culture conditions and results are spatially averaged, masking important single cell and molecular level information. Atomic force microscopy and pipette aspiration are cell culture compatible, but low throughput. The goal of the proposed research is to develop a high throughput microfluidic rheometer for systematic studies of tumor mechanics and invasion in a physiologically realistic 3D setting and compatible with dynamic optical imaging at single cell and spheroid levels. We will deliver a set of principles that govern tumor mechanics and its relation with invasion. We postulate that tumor mechanics is a key predictor for tumor invasiveness. The proposed project is innovative because it represents the first generation of microfluidic rheometers that are capable of full mechanical testing for tumor mechanics studies, and at the same time compatible with tumor invasion experiments. Tools developed here can be easily extended to use for other living materials, and lessons learned here will eventually lead to knowledge important for developing novel diagnostic or/and treatment strategies for cancer.