Microfluidics for synthetic biology

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Synthetic biology describes the process of engineering a cell for new or improved functionality. In recent years, there has been a rapid surge in the use of synthetic biology tools to enable scientists to create biological entities not yet present natural world. Examples include several landmark genomic projects that have brought-forth essential synthetic biology tools, such as the revolution of `next-generation' sequencing, and the discovery of CRISPR-Cas9, regarded  as one of the most important contribution to the field of synthetic biology and has ushered in a new era of rapid gene editing. Despite this flood of new biological systems and technologies, the process of developing these new biological systems is extremely labour-intensive, expensive and less-than deterministic. In many cases, high-throughput experimentation must be carried-out to provide a high-resolution picture of how a system's parameters interact while also delivering in the shortest possible timeframe. To categorize different stages of work, synthetic biology has adopted the design-build-test-learn cycle of engineering. It is through many rounds of this cycle that researchers can engineer a biological system. Even today where industrial manufacturing is largely automated, much of the work in synthetic biology research is done by hand through frequent pipetting and transferring samples from one platform to another. As a result, technique is learned by trial-and-error, while documented protocols are subject to interpretation. Microfluidics have emerged to provide solutions to "close-the-loop" in synthetic biology lending platforms for automating multiple aspects of the cycle and many different applications related to synthetic biology. These platforms are ideal for processing liquid samples in synthetic biology considering the expensive reagents, the tedious liquid processing workflows, the small footprint, and portability of these platforms makes them especially suitable for automating this process. In this proposal, I outline my research program unified by the theme of automating synthetic biology using microfluidics. The program spans two streams:  (1) I describe how we automate the build-part of the cycle, describing automation of synthesis, assembly, and delivery of large constructs and to gene edit cells on-demand with high-fidelity. (2) I describe how we integrate microfluidics for several synthetic biology test applications and how we can learn to derive new (re)designs. For instance, we will describe our innovative efforts in directed evolution of enzymes, optogenetics to control gene expression for metabolic engineering, and design new biosensors for detecting food spoilage and viral-based diseases. Overall, this program is poised to have significant impact leading to groundbreaking advances in the biotechnology sector with enormous long-term benefits for areas like human health and bio-energy in Canada and other countries worldwide.