Electrically-enhanced modular microfluidics for single-cell analysis

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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.