Automation of Synthetic Biology and Genome Engineering Protocols using Digital Microfluidics

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Nick Trotta, Arjun Sudarsan, Sarah Negri, Sri Punnamaraju, Melissa Sandahl, Lisa Bukovnik, Michael Pollack

Advanced Liquid Logic, United States

Large-scale genome engineering represents a broad group of technologies, all of which stand to impact the manufacturing of a range of biological and chemical products. While the power of these methods to increase the production of biologically-driven manufacturing processes has been previously demonstrated, they are often developed and optimized toward a single target, or single methodology. For example Multiplex Automated Genome Engineering, or MAGE has been used to simultaneously engineer all 20 genes in an important isoprenoid pathway in Escherichia coli to produce record lycopene yields. Automating this method required a range of custom instrumentation, not suited to other genome engineering methods or targets without dramatic reconfiguration. Therefore, a platform does not currently exist that enables a broad range of genome engineering methods directed towards a diverse range of biomanufactured products. Advanced Liquid Logic (ALL) has developed a powerful software-programmable liquid handling technology called digital microfluidics. ALL is currently collaborating with a number of lead users to automate a broad range of synthetic biology and genome engineering protocols. These include: gene synthesis using oligonucleotide building blocks, quality assessment of synthetic genes, cell-free gene circuits and targeted genome engineering. Specific features of the ALL platform make it ideal for these applications. Software programmability provides a high degree of application flexibility, allowing users to generate multiple bioassay protocols which can be run on the same instrument and disposable cartridge. In addition, a new software development architecture is under development, allowing real-time monitoring and intervention of each reaction droplet. The platform also provides support for a range of molecular biology processes, including thermocycling, magnetic bead operations and optical detection (including both fluorescence and chemiluminescence). Coupling general molecular biology capabilities, with software-based control over hundreds of reaction droplets provides an automation platform uniquely suited to both synthetic biology and genome engineering.