Developing Functional Life-On-Chip Microsystems for Understanding Cancer Biology

癌症是发达国家的第二大死亡原因，仅在加拿大就花费了数十亿美元的医疗费用。癌症研究进展的主要障碍包括缺乏在实验室中研究癌症生物学的有用和信息丰富的实验方法，以及缺乏在临床上为患者选择正确治疗的工具。因此，迫切需要开发新的创新工具和方法，以改变我们对癌症研究和临床治疗的方法。我的研究项目的主要目标是为生物学家和临床医生创建一类新的实验工具，称为“芯片生命”（life-on-chip，缩写为MEMS）微系统，它可以在微型芯片中模拟细胞，组织和器官的行为和功能，这些芯片可以放在你的手掌上。这类新的工具将大大增加我们的实验工具包，通过提供与实际活组织和器官的更好的相似性，同时消除对动物试验的需要。为了开发和推进这些微系统，我的研究计划将结合联合收割机在工程和生物领域的专业知识，采用流体动力学，机械工程设计，微细加工，计算方法，细胞生物学和先进的显微镜的原则。我提出的研究计划侧重于开发和表征三种新的微系统，这些微系统将提供新的方法来研究癌细胞如何与邻近细胞类型进行通信，血管如何在肿瘤中发育，以及癌细胞如何在转移扩散过程中粘附到不同的组织。这项研究将导致新的工程设计概念和原则，并创造关于如何设计最佳微系统以研究癌症生物学的新知识。

Cancer is the second leading cause of death in the developed world, costing billions of dollars in health care costs in Canada alone. Major barriers to progress in cancer research include the lack of useful and informative experimental methods for studying cancer biology in the lab, and lack of tools for choosing the right therapy for the patient in the clinic. Thus, there is an urgent need to develop new, innovative tools and methods that can change our approach to cancer research and clinical therapy. The primary goal of my research program is to create a new class of experimental tools for biologists and clinicians called "life-on-chip" (LOC) microsystems, which can mimic cell, tissue, and organ behavior and function in miniaturized chips that can fit on the palm of your hand. This new class of tools will significantly add to our experimental toolkit by providing improved resemblance to actual living tissues and organs while eliminating the need for animal testing. To develop and advance these LOC microsystems, my research program will combine expertise in both engineering and biology fields, employing the principles of fluid dynamics, mechanical engineering design, microfabrication, computational methods, cell biology, and advanced microscopy. My proposed research plan focuses on the development and characterization of three new LOC microsystems that will offer new ways to study how cancer cells communicate with neighboring cell types, how blood vessels develop in tumors, and how cancer cells adhere to different tissues during metastatic spread. The research will lead to novel engineering design concepts and principles, and create new knowledge on how to engineer optimal LOC microsystems for studying cancer biology.