Development of Cell Culture Processes on Digital Microfluidic Platforms

In vitro microenvironments used for culturing and studying living cells have remained virtually unchanged for the last five decades. Mammalian cells are routinely seeded as monocultures onto rigid, homogeneous, two dimensional substrates – systems with limited physiological relevance. Microfluidics has the potential to significantly improve cell models to better mimic native tissue or disease states in addition to a host of other benefits such as improved throughput, reduced consumable requirements and seamless integration with a number of analysis techniques. Digital microfluidics, a fluid handling technique which manipulates discrete droplets over micro-electrode patterned surfaces, may be a valuable tool for a number of cell applications incorporating all of the above potential advantages. Cell culture and analysis is a new application for digital microfluidics – the first report of such was in 2008. As a result, a number of technical impediments must be addressed before cells can be effectively and routinely studied on these microfluidic devices. These impediments include: a) rapid device failure due to protein biofouling on hydrophobic device surfaces, b) the unexplored possibility of detrimental effects on cell fitness arising from the electrokinetic manipulation of droplets and c) the lack of robust iii systems capable of long term automated culture and integrated analysis of cells. The aim of the work described in this thesis is to advance digital microfluidics for biologically relevant cellular culture and analysis by addressing each of these challenges. The technical advancements gained from these studies can then be used to develop a proof-of-concept digital microfluidic platform for modeling liver tissue. In summary, this work describes advances towards physiologically-relevant culture and analysis of living cells on digital microfluidics, a technology which has the potential to become a valuable tool for the biomedical research community.Ph