Synthetic biology opens many new doors for researchers. Core facilities and other dedicated synthetic biology labs now permit researchers to design large numbers of synthetic construct combinations for testing and have them made to order quicker, more easily, and to a higher standard than doing it themselves. The challenge for synthetic biology labs now is to scale up their workflows to meet the growing demand for high-throughput construct assembly and validation, whilst maintaining high quality levels. Increasing throughput of the standard synthetic biology workflow presents a major challenge. Each constituent DNA part must be individually stored but remain accessible on demand. Core facilities typically house hundreds of thousands of components and completed constructs, storing, tracking and retrieving each one individually as required. Repeated cycles of freeze/thaw reduce sample integrity over time.
The number of man-hours required for manually retrieving components, setting up assembly reactions and validating constructs is immense. Assembly time and cost is one of the main bottlenecks in synthetic biology, limiting the number of constructs it is feasible to generate per project. High-density, automated storage and retrieval of individual 2D-barcoded samples allows quick and easy access to DNA components. Automation of liquid handling enables miniaturised construct assembly to nanolitre scale. In this way, sample and reagent volumes can be reduced, and speed, accuracy and reproducibility can all be improved from manual methods. This application note describes an automated, high-throughput workflow that has been integrated for the generation of synthetic DNA constructs at GeneMill, University of Liverpool – led by Dr James Johnson.