Microfluidic and Nanofluidic Biotechnologies for Applications in the Health Sciences

疾病的性质，从它的生物学起源到它在病人身上的识别和管理，本质上是复杂的。在开发新的生物物理分析能力方面的进展为研究人员提供了对疾病的生物起源的新见解，同时使医生能够使用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控生物技术，通过利用微纳尺度的现象来缓解现有分析平台的缺点。虽然能够执行复杂样品处理程序的微流控设备可以缓解与标准实验室实践相关的效率和重复性问题，但芯片上分析能力(生物传感器)的集成极大地增强了功能。这些所谓的“芯片实验室”能够进行复杂的样品处理，而芯片上的探测器或生物传感器提供反馈。这一多学科研究计划将探索三个互补的主题，通过提议开发微流控平台，提供对疾病细胞行为的洞察，并带来新的疾病诊断和基于细胞的治疗机会。具体地说，将开发一种能够捕获和跟踪单个细胞大小的微流控体积传感器，并用于量化与遗传异常和疾病状态有关的细胞生长速度。众所周知，癌细胞生长速度的异常会导致肿瘤的发展。这个微流控平台将进一步实现各种化疗毒剂(药物)影响下的疾病细胞生长速度的关联。对于诊断应用，集成在微流控平台中的纳米孔传感器将用于检测与疾病相关的生物标志物(蛋白质)。纳米孔传感器具有单分子灵敏度，当与新的生化分析相结合时，能够对蛋白质进行高度多元化的检测。当与微流体集成时，性能可以得到增强，同时引领实现真正便携的护理点诊断平台。第三，在细胞再生医学应用的推动下，将开发一种能够包裹干细胞和祖细胞的微流控技术。通过将细胞包裹在特殊配方的水凝胶中，我们希望显著提高细胞的存活率、植入率和治疗效率。虽然这项研究计划专注于微流控技术的发展，但这项工作显然是出于特定的生物医学应用。事实上，我们与其他研究人员和行业合作伙伴保持着几个协同合作，允许研究生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控技术方面的创新，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.