Microfluidic and Nanofluidic Biotechnologies for Applications in the Health Sciences

疾病的性质，从其生物学起源到其在患者中的识别和管理，本质上是复杂的。新型生物物理分析能力的进步为研究人员提供了了解疾病生物学起源的新途径，同时为医生提供了更有效的诊断工具和治疗方案。这个发现项目旨在开发新的微流体生物技术，通过利用微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控设备可以减轻与标准实验室实践相关的效率和可重复性问题，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“片上实验室”能够处理复杂的样品，而片上探测器或生物传感器提供反馈。这个多学科研究项目将探索三个互补的主题，通过提出微流控平台的发展，提供对患病细胞行为的洞察，并导致新的疾病诊断和基于细胞的治疗机会。具体来说，一种能够捕获和跟踪单个细胞大小的微流体体积传感器将被开发出来，并用于量化与遗传异常和疾病状态相关的细胞生长速度。众所周知，癌细胞生长速度的异常会导致肿瘤的发展。该微流控平台将进一步实现各种化学毒物（药物）影响下病变细胞生长速率的相关性。对于诊断应用，集成在微流控平台内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，当与新型生化分析相结合时，它能够高度多路检测蛋白质。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的即时诊断平台。第三，以细胞为基础的再生医学应用为动力，将开发一种能够包封干细胞和祖细胞的微流体技术。通过将细胞包裹在特殊配方的水凝胶中，我们期望显著提高细胞活力、植入和治疗效果。虽然这个研究项目的重点是微流体技术的发展，但这项工作显然是由特定的生物医学应用驱动的。事实上，我们与其他研究人员和工业合作伙伴保持着几项协同合作，使研究生能够磨练他们在应用生物物理学（技术开发）方面的技能，同时提供多学科影响。从长远来看，这项工作不仅将提供分析微流控技术的创新，而且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.