Microfluidic and Nanofluidic Biotechnologies for Applications in the Health Sciences

疾病的本质，从其生物学起源到患者的识别和管理，本质上是复杂的。新型生物物理分析能力的发展为研究人员提供了对疾病生物起源的新见解，同时为医生提供了更有效的诊断工具和治疗方案。该发现计划旨在开发新的微流体生物技术，通过利用微米和纳米尺度的现象来减轻现有分析平台的缺点。虽然能够执行复杂样品操作程序的微流体装置可以减轻与标准实验室实践相关的效率和再现性问题，但芯片上分析能力（生物传感器）的集成大大增强了功能。这些所谓的“芯片实验室”能够进行复杂的样品处理，同时芯片上的检测器或生物传感器提供反馈。该多学科研究计划将探索三个互补的主题，提出开发微流体平台，以深入了解患病细胞的行为，并带来新的疾病诊断和基于细胞的治疗机会。具体而言，将开发一种能够捕获和跟踪单个细胞大小的微流体体积传感器，并用于量化与遗传异常和疾病状态有关的细胞生长速率。众所周知，癌细胞生长速度的减慢会导致肿瘤的发展。该微流体平台将进一步实现在各种化学毒性剂（药物）的影响下患病细胞的生长速率的相关性。对于诊断应用，集成在微流体平台内的纳米孔传感器将用于检测疾病相关的生物标志物（蛋白质）。具有单分子灵敏度，纳米孔传感器在与新型生化测定组合时能够高度多重检测蛋白质。当与微流体集成时，性能可以得到增强，同时引领真正便携式护理点诊断平台的发展。第三，受基于细胞的再生医学应用的激励，将开发能够封装干细胞和祖细胞的微流体技术。通过将细胞包封在特殊配制的水凝胶中，我们期望显著提高细胞活力、植入和治疗功效。虽然这项研究计划的重点是微流体技术的开发，但这项工作显然是由特定的生物医学应用所推动的。事实上，我们与其他研究人员和工业合作伙伴保持着多项协同合作，使研究生能够在提供多学科影响的同时磨练他们在应用生物物理学（技术开发）方面的技能。从长远来看，这项工作不仅将提供分析微流体技术的创新，还将寻求改善加拿大人的健康。

The nature of disease, from its biological origins to its identification and management in patients, is inherently complex. Advances in the development of novel biophysical analytical capabilities provide researchers access to new insight into the biological origins of disease, while empowering doctors with more efficient diagnostics tools and treatment options. This Discovery program is aimed at developing new microfluidic biotechnologies that mitigate the shortcomings of existing analytical platforms by exploiting micro- and nano-scale phenomena. While microfluidic devices capable of performing complex sample manipulation procedures can mitigate efficiency and reproducibility issues associated with standard laboratory practices, the integration of on-chip analytical capabilities (biosensors) greatly enhances functionality. These so-called “labs-on-a-chip” are capable of complex sample processing while on-chip detectors or biosensors provide feedback. This multidisciplinary research program will explore three complementary themes, by proposing the development of microfluidic platforms that provide insight into the behavior of diseased cells, and that lead to new disease diagnostics and cell-based treatment opportunities. Specifically, a microfluidic volume sensor capable of trapping and tracking the size of individual cells will be developed and used to quantify cellular growth rate with respect to genetic abnormalities and disease state. Abnormalities in the growth rate of cancer cells are well-known to lead to tumor development. This microfluidic platform will further enable the correlation of growth rate of diseased cells under the influence of various chemotoxic agents (drugs). For diagnostics applications, nanopore sensors integrated within the microfluidic platform will be used to detect disease-related biomarkers (proteins). With single molecule sensitivity, nanopore sensors are capable of highly multiplexed detection of proteins when combined with novel biochemical assays. When integrated with microfluidics, performance can be enhanced while leading the way towards a truly portable point-of-care diagnostics platform. Thirdly, motivated by cell-based regenerative medicine applications, a microfluidic technology capable of encapsulating stem and progenitor cells will be developed. By encapsulating cells in specially formulated hydrogels, we expect to significantly increase cell viability, engraftment and treatment efficacy. While this research program focuses on microfluidic technology development, the work is clearly motivated by specific biomedical applications. In fact, we maintain several synergistic collaborations with other researchers and industrial partners that allow graduate students to hone their skills in applied biophysics (technology development) while providing multidisciplinary impact. In the long-term, this work will not only provide innovations in analytical microfluidic technologies but also seeks to improve the health of Canadians.