Process development in biomanufacturing is still labor-intensive and time-consuming due to the dynamic nature of the system. To bring a high-quality product to the market in minimum time, it is highly desirable to optimize the bioprocess expeditiously. Though shake flasks are still widely used in initial stages of process development, bioreactors are preferred as they offer relatively stable and controlled condition for cell growth. Micro-bioreactors have been widely used in strain screening and media optimization studies. However, with such a smaller volume, the process cannot be easily scalable to benchtop bioreactors. Here we present the application of parallel mini-bioreactors (total volume 100 mL, max. working volume 70 mL) enabled with optical sensors, measuring pH and DO critical process parameters for biomanufacturing. A novel non-invasive CO2 sensor is also deployed for monitoring the DCO2 concentration in real time. A supervisory program is developed using LabVIEW to monitor and control the process variables at desired set points. We demonstrated the application of this low-cost mini-bioreactor using a case study of optimizing the production of an anti-malarial precursor drug (amorphadiene and/or artemisinic acid) from the culture of recombinant yeast Yarrowia lipolytica. This platform can be easily adapted for culturing a wide variety of micro-organism for hassle-free, cheaper and faster process optimization.

High-throughput mini-bioreactor platform for optimizing production of anti-malarial precursor drug from an engineered yeast Yarrowia lipolytica

2019 Spring National Meeting

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