Microfluidics for automating and integrating synthetic biology

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Synthetic biology has been used to engineer complex biological systems in areas such as therapeutics, bioenergy, and biological materials. However, this has been limited by two challenges: scalability and integrating automation of the synthetic biology Design-Build-Test-Learn workflow. Current research laboratories are equipped with robots that are aimed to accelerate synthetic biology and provide high-throughput solutions; however, they require more effort to instruct a robot to perform a new task than saving the researcher time in performing the task. Furthermore, they are expensive -- well outside of the budgetary reach of many scientific laboratories and have large footprints making it difficult for systems integration. Therefore, there is a need to create new automation technologies to expedite the synthetic biology workflow with the advantages of reducing costs and time while increasing the complexity of the biological systems that are created. In response to this challenge, the proposed research program is to develop microfluidic automation platforms for synthetic biology. This new tool will be powered by digital microfluidics (DMF), a fluid handling technique in which ~nL volumes can be manipulated in parallel on a patterned array of electrodes. To facilitate high-throughput applications, we will integrate DMF with droplet-in-channels - a two-phase system where it uses immiscible phases to create emulsions of monodisperse droplets that can act as microreactors containing a single cell or a cocktail of chemical reagents. To facilitate automation, these two microfluidic paradigms will be used together to create droplets containing DNA libraries that are transformed into bacteria or yeast and the functionality of these variants will be evaluated on the basis of directed evolution screening. This research program spans two streams: (1) development of a Microfluidic Automation and Characterization Station (M.A.C.S), and (2) microfluidic integration of the synthetic biology cycle. The proposed research program will enable new automation technologies with reduced costs, time, and manual intervention; in addition, the automation system will be inexpensive, will have no moving parts and a small laboratory footprint. In parallel, with developing microfluidics for synthetic biology, a M.A.C.S will enable (a) automatic reagent delivery to the microfluidics, (b) automation of droplet movement, (c) in-line detection system for rapid analysis. This system will be characterized by implementing synthetic biology to discover newly engineered microbes for biofuel production. If successful, this method could transform the field of automation and synthetic biology, and making it accessible for basic and applied scientists to solve problems that could transform other areas such as manufacturing, food production, and healthcare in Canada (and world-wide).