The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to develop technology that will enable robust, contamination-free, continuous biomanufacturing. While biomanufacturing may be one of the most technologically complex and profitable industries, the underlying production process, batch fermentation, has not changed in decades. In theory, continuous fermentation would decrease operational cost and increase production capacity. However, owing to the high risk of contamination, continuous fermentation is considered unreliable and is rarely used. The proposed technology solves this issue and enables contamination-free, continuous fermentation. Successful implementation of continuous fermentation facilitates automated production and paves the way for future technological development in continuous product purification and recovery. The reduced operational cost is essential for the economic viability of bio-based commodity chemicals such as bioplastics, as their market demand depends primarily on their price competitiveness with petroleum-derived counterparts. The proposed technology also eliminates the use of antibiotics in fermentation, which in turn alleviates antibiotic misuse and promotes a positive environmental and health impact. <br/><br/>The intellectual merit of this SBIR Phase I project is to explore the feasibility of using a biocide/biocide-resistant system to prevent and treat microbial contamination during continuous biomanufacturing. Microbial contamination in biomanufacturing processes is a major concern, as it results in loss of productivity, time, and money. In addition, it restricts the production mode to slow batch fermentation, and prohibits the implementation of continuous fermentation. The proposed technology solves the contamination problem, as a biocide will inhibit the invading microbial and viral contaminants and a biocide-resistant enzyme will protect the processing hosts. The proposed Phase I research will address the technical challenges by using classical molecular biology and synthetic biology techniques. The first objective is to demonstrate that the proposed technology will provide biocide resistance to bioplastics-producing organisms while inhibiting the outgrowth of contaminants. The second objective is to show that the proposed technology can be used to prevent and treat contamination in continuous fermenters. The final objective is to fine-tune the biocide/biocide-resistant system to demonstrate the technology will not adversely affect the production yield and product quality in continuous fermenters. If successful, future Phase II development will be conducted in pilot and industrial-scale reactors to further optimize the technology.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.