Electrically-enhanced modular microfluidics for single-cell analysis

单细胞分析和单个细胞的动态研究在样本高度异质性的细胞生物学研究中是至关重要的（例如血液学和干细胞研究）。微流体精确控制少量流体的能力使其成为单细胞分析的完美技术。然而，诸如对外部设备的依赖和有限的操作灵活性等挑战阻碍了它们在现实生活中的广泛应用。我的研究项目侧重于开发先进的电子技术，并将其纳入微流体，使单细胞分析无需设备和通用技术。电方法由于其高灵敏度、无标签性和易于与微流体集成而具有优势。我的短期目标将解决我的领域中两个长期存在的挑战i)消除对片外样品制备的需要ii)通过制作由离散可重构模块组成的模块化平台来增强微流体系统的应用灵活性。生物细胞表现出频率依赖的介电特性，已知这与它们的生理有关。这是两种著名的电池分析技术的基础，介质电泳（DEP）和电阻抗谱（EIS），它们完全基于细胞的固有介电特性来询问细胞。我将开发新的基于DEP和ei的技术嵌入到微流体中，以执行芯片上的单细胞样品制备任务，如细胞富集，细胞分离和细胞裂解。我将建立具有细胞处理和电测量能力的模块化微流体平台的主要规则，并为开发模块化电增强单细胞分析仪奠定基础。该系统最初将由三个样品制备模块组成：多频EIS-DEP细胞富集模块、DEP细胞分选模块和DEP单细胞分离模块。模块将单独设计、制造和组装在一起，形成完整的微流体系统。这个模块化平台将是我的计划的基石，并将随着时间的推移，纳入更先进的电气模块与嵌入式电子样品制备和细胞分析。这项研究推进了基于电的细胞分析技术，并为低成本、通用和独立的单细胞分析技术的发展奠定了基础。这将是细胞生物学和细胞机制研究的变革，促进实质性的细胞发现。开发的电气方法也将影响到便携性和成本很重要的护理点应用的传感器领域。此外，该项目将培养具有生物应用微技术专业知识的高素质HQP，为加拿大快速发展的跨学科产业做出贡献。

Single-cell analysis and dynamic study of individual cells is paramount in cell biology research where samples are highly heterogeneous (for example hematology and stem-cell research). The capability of microfluidics in precise control of small amount of fluid has made it the perfect technology for single-cell analysis. However, challenges such as dependency on external equipment and limited operation flexibility has impeded their widespread real-life applications. My research program focuses on developing advanced electrical techniques and incorporating them into microfluidics to make equipment-free and versatile technologies for single-cell analysis. Electrical methods are advantageous due to their high sensitivity, label-free nature, and facile integration with microfluidics. My short-term objectives will address two long-standing challenges in my field i) eliminating the need for off-chip sample preparation and ii) enhancing the application flexibility of microfluidic systems by making modular platforms consisting of discrete reconfigurable modules. Biological cells exhibit frequency-dependent dielectric characteristics that are known to be correlated with their physiology. This has been the basis of two well-known electrical cell analysis techniques, dielectrophoresis (DEP) and electrical impedance spectroscopy (EIS), which interrogate cells exclusively based on their intrinsic dielectric properties. I will develop new DEP- and EIS-based techniques embedded into microfluidics to perform on-chip single-cell sample preparation tasks, such as cell enrichment, cell isolation, and cell lysis. I will establish primary rules for making modular microfluidic platforms with cell handling and electrical measurement capabilities and lay foundations for developing a modular electrically-enhanced single-cell analyser. The system will initially consist of three sample preparation modules: a multi-frequency EIS-DEP cell enrichment module, a DEP cell sorting module, and a DEP single-cell isolation module. Modules will be individually designed and fabricated and assembled together to form the complete microfluidic system. This modular platform will be the cornerstone of my program and will grow over time to incorporate more advanced electrical-based modules with embedded electronics for sample preparation as well as cell analysis. This research advances electrical-based techniques for cell analysis and lays foundations for development of low-cost, versatile, and stand-alone single-cell analysis technologies. This will be transformative in cellular biology and cell mechanism studies, facilitating substantial cellular discoveries. The developed electrical methods will also impact the area of sensors for point-of-care applications where portability and cost are important. In addition, this program will train high-caliber HQP with expertise in micro-technologies for bio-applications who will contribute to such fast-growing interdisciplinary industries in Canada.