In vitro Biomanufacturing on a Chip (iBOC): Leveraging Nanophotonic Sensors for Rapid Prototyping of Bioproduction Pathway

Biomanufacturing is a transformative branch of manufacturing that leverages biological systems, such as living cells or enzymes, to produce a wide array of products, from pharmaceuticals to biofuels. The commercialization of biomanufacturing faces challenges, including slow strain development, scale-up production difficulties, and high costs of downstream processing. Addressing these issues, this project introduces the in vitro Biomanufacturing on a Chip (iBOC), which enhances in vitro prototyping by providing rapid sensing feedback to optimize enzyme combinations in metabolic pathways. This approach accelerates strain development timelines, reduces reliance on empirical methods, and improves the scalability and cost-effectiveness of biomanufacturing. The project will significantly benefit the US bioeconomy by enabling the efficient production of economically viable bioproducts, strengthening domestic biomanufacturing capabilities, and reducing reliance on foreign imports. Moreover, transitioning to bioproduction has the potential to cultivate a more resilient economy. The iBOC technology will integrate a photonic crystal biosensor and a surface-enhanced Raman scattering sensor to monitor cell-free synthesized enzymes and metabolites, respectively. The microfluidic component will enable the assembly and testing of target metabolic pathways by providing precise control over the mixing of gene cassettes. The iBOC's capabilities include evaluating metabolic pathways, identifying rate-limiting steps, and optimizing metabolic flux to achieve a balanced distribution of metabolites. If successful, metabolic engineers can utilize the iBOC system to prototype their biosynthesis pathways, expedite the cycle of design-built-test-learn, and guide the development of cell-based bioproduction. The project will focus on optimizing the dopamine pathway as a representative example. To maximize the project's impact, the proposed research activities will be seamlessly integrated with educational and outreach initiatives. Collaboration with the recently funded EPSCoR Center (Chemurgy 2.0) at Iowa State University will facilitate the training of students in bioproduction expertise, thereby expanding the nation's workforce in biomanufacturing. The team will also work with the Chemurgy 2.0 Center to enhance the existing biology curriculum for K-12 students and stimulate their interest and involvement in STEM. 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.