Bacteria are a common host to produce diverse biologics. Synthesis of recombinant proteins using bacterial hosts entails multiple steps including culturing, disruption, and subsequent isolation and purification of the desired product.  

For industrial operations, each step requires a sophisticated and delicate infrastructure to ensure efficiency and product quality. While critical for producing molecules in large amounts, this format is not flexible or economically suited for producing or characterizing diverse biologics in small scale. Moreover, standard biomanufacturing is not accessible in remote or underdeveloped areas that lack the basic infrastructure and personnel with necessary technical training. Therefore, there is a critical need to develop technologies for versatile and scalable production of diverse biologics on demand, as well as subsequent analysis and purification. 

By exploiting cell-material feedback, YOU Lingchong, a Professor of Biomedical Engineering at Duke University, and Associate Prof DAI Zhuojun at Shenzhen Institutes of Advanced Technology of Chinese Academy of Sciences developed a concise platform to achieve versatile production together, analysis, and purification of diverse proteins and protein complexes.  

The core of our technology is a microbial swarmbot, which consists of a stimulus-sensitive polymeric microcapsule encapsulating engineered bacteria. By sensing the confinement, the bacteria undergo programmed partial lysis at a high local density. Conversely, the encapsulating material shrinks responding to the changing chemical environment caused by cell growth, squeezing out the protein products released from bacterial lysis. This platform is then integrated with downstream modules to enable quantification of enzymatic kinetics, purification of diverse proteins, quantitative control of protein interactions, and assembly of functional protein complexes and multi-enzyme metabolic pathways.  

The study demonstrates the use of the cell-material feedback to engineer a modular and flexible platform with sophisticated yet well-defined programmed functions. The operation is simple and can be conducted after minimal training. These properties are essential for a number of application contexts, such as personalized drug synthesis and accessible biomanufacturing in remote areas.