UC San Diego

The rise of DNA sequencing and synthesis technologies over the past two decades has ushered in a new wave of forward engineering genetic circuits, synthetic biology. Synthetic biology has since been deployed for applications spanning therapeutics, industrial chemical biosynthesis, and environmental sensing. Coupled with advances in genomics and systems biology, synthetic biology has revolutionized our ability to investigate biological networks. Further utilized with the fine-tuned experimental control of microfluidics, synthetic biology has enabled the precise interrogation of single nodes in these biological networks. The emergence of genome-scale microfluidic devices has bridged the gap between the multiplexing of -omics technology and the dynamics of microfluidics. Towards this end, we have developed an elegant, simple microfluidic platform capable of monitoring the temporal gene expression of 2,176 unique microbes with both research and industrial application. In Chapter 1, I provide a brief overview of synthetic biology and microfluidics in the context of biological research. In Chapter 2, I describe the high-throughput microfluidic platform we have engineered and the protocol for building these devices. In Chapter 3, I demonstrate the platform’s utility as an environmental biosensor and research tool, where the dynamics of 1,807 E. coli GFP-promoter strains coupled with machine learning algorithms are used to detect the presence of six heavy metals in real-time in both laboratory and real-world settings. Finally in Chapter 4, I show the device’s application for the dynamical screening of synthetic gene circuit libraries. In all, I highlight the need for the further development of such multiplexed microfluidic platforms and demonstrate their utility for biological research, synthetic gene circuit engineering, and environmental biosensing.