Engineered Microbial Swarmbots with Safeguard Mechanism

Engineered bacteria have great potential for diverse applications in medicine, bioremediation and energy. These applications, however, have been limited by the safety concern over unanticipated effects of engineered bacteria on human health or environment. To address this issue, we have developed a prototype microbial swarmbots (MSB) technology to implement a safeguard mechanism and prevent unintended proliferation from controlled environment. We integrated synthetic biology, microencapsulation, and microfluidics to construct this technology. Specifically, the gene circuit we constructed is a minimal self-addition circuit to program density-dependent survival of the engineered bacteria: they can only survive at a sufficiently high density. When turned ON, the circuit will allow survival of encapsulated bacteria, which have a high local density, but not the escaped bacteria, which have a low density. By encapsulating them in the microcapsules, the bacteria only grew inside the capsule not the outside as expected, when treated by appropriate concentration of antibiotic pulsing. Our mathematic models predicted all the MSB dynamics and enabled the optimal modulation in predictive manners. We further developed a microfluidic platform to monitor and quantify the dynamics, which confirmed the design features of MSB. Our work demonstrates a novel, integrated approach to achieve robust control of bacterial dynamics and has implications for autonomous synthesis and delivery of therapeutic proteins.