Development of Paper-Based Microfluidic Biosensors for Medical Diagnostics

诊断性生物标志物的准确检测对疾病的控制和治疗具有重要意义。生物相关的微流控装置由于其在生物分析方面的明显优势，作为一种使能工具，具有巨大的潜力，可以改变医学诊断的实践。纸基微流控技术作为一个新兴领域，在开发低成本、便携的诊断平台方面具有广阔的前景。与传统的微流体装置不同，PMF装置通过毛细管作用将流体分布在图案纸通道中，能够在资源和基础设施有限的情况下检测疾病标志物。目前，PMF技术的许多方面在很大程度上尚未得到充分探索。本项目的长期研究目标是建立PMF研究的理论和技术框架，推动PMF技术在诊断中的实际应用，旨在开发新型PMF生物传感器，以低成本、高通量检测临床相关生物标志物。理论和技术创新将通过以下方面进行：(1)纸面通道中毛细管流动的流体动力学建模，这将产生通用的设计指南；(2)发明和/或开发新型流体控制元件和生物传感技术，以实现卓越的设备性能；(3)通过PMF大规模集成开发多功能、高度集成的生物传感器分析，以实现高通量应用。该计划的一个独特贡献将是开发PMF大规模集成的系统方法，这可能最终导致高密度PMF器件的实现。本研究中开发的新知识、创新技术和首创的生物传感设备将显著推进PMF领域的最新技术，并为改进现有诊断系统（例如，在更低成本、更高通量和更好的可及性方面）提供有希望的解决方案。该研究项目还将为培养工程、生物技术和医学方面的高素质人才提供良好的多学科环境。

Accurate detection of diagnostic biomarkers is important to control and treatment of diseases. Biologically relevant microfluidic devices have enormous potential, as enabling tools, to change the practice of medical diagnostics, due to their apparent advantages for bioanalysis. Paper-based microfluidics (PMF), as an emerging field, is particularly promising for developing low-cost, portable diagnostic platforms. Different from conventional microfluidic devices, PMF devices distribute fluids in patterned paper channels by capillarity, and are capable of detecting disease markers with limited resources and infrastructures. Currently, many aspects of PMF technology are largely underexplored. With long-term research goals of building up a theoretical and technological framework for PMF research and advancing PMF technology towards practical use in diagnosis, this research program aims to develop novel PMF biosensors to target low-cost, high-throughput detection of clinically relevant biomarkers. Theoretical and technological innovations will be made through: (1) fluid dynamics modeling of capillary flows in paper channels, which will produce generic design guidelines; (2) invention and/or development of novel fluid-control components and biosensing techniques to enable excellent device performance; and (3) development of multifunctional, highly-integrated biosensor assays through PMF large-scale integration, for high-throughput applications. A unique contribution of this program will be the development of a systematic approach to PMF large-scale integration, which could eventually lead to the realization of high-density PMF devices. The new knowledge, innovative techniques, and first-of-their-kinds biosensing devices developed in this research will significantly advance the state of the art in the field of PMF, and provide promising solutions to the improvement of existing diagnostic systems (e.g., in terms of lower cost, higher throughput, and better accessibility). This research program will also offer an excellent multidisciplinary environment for training highly qualified personnel in engineering, biotechnology, and medicine.