Enhanced Pichia Strain and Process Development with Microbioreactors
VALIDOGEN integrates advanced microbioreactor technology to maximize the efficiency of its UNLOCK PICHIA® platform supporting the company’s
- Advanced Pichia pastoris strain selection and development program
- Bioreactor process optimization workflows for enhanced protein production
Key Advantages of Microbioreactors* for VALIDOGEN’s Strain Selection and Process Development
- Time- and resource-saving intermediate step between microscale and bioreactor cultivation
- An aid to effectively narrow promising clones identified in microscale screening
- Tightly controlled bioreactor-like conditions for both methanol-induced and methanol-free protein production
- High predictability for bioreactor cultivation processes
- Simultaneous optimization of multiple cultivation conditions using Design of Experiment (DoE) methodologies
*High-throughput 1 mL well microscale cultivation device capable of controlling temperature, pH value and feed rate, and monitoring level of dissolved oxygen.
Streamlining Pichia Strain Development with Microbioreactors
VALIDOGEN enhances its strain engineering capabilities by incorporating microbioreactors as a high-efficiency tool for optimization of recombinant protein production in Pichia pastoris. To commence strain development and ensure the early identification of highly productive strains VALIDOGEN leverages its high-throughput microscale screening in 96-deep well plates, where the productivity of thousands of clones is assessed in minimal time. However, when a larger number of high-potential clones emerge from microscale screening, microbioreactor cultivations provide a valuable intermediate validation step under precisely controlled conditions. This process effectively narrows down candidates or directly identifies the final production strain before confirming performance in larger bioreactors.
Key Benefits of VALIDOGEN’s High-Throughput Screening
- Thousands of clones screened in parallel in minimum time
- Fast and reliable identification of high-performance production clones
- Scalability of results from microscale screening to bioreactors
Enhancing Bioreactor Process Development with Microbioreactors
Beyond their role in strain selection, microbioreactors also serve as a cost-effective and scalable alternative to traditional lab-scale bioreactors, playing a crucial role in optimizing cultivation conditions and refining protein expression processes. With precise control over temperature, pH, feed strategies, and nutrient supply, microbioreactors support advanced DoE-driven process optimization, reducing time and resource expenditure.
CASE STUDY: Microbioreactor-Driven Bioprocess Optimization boosting VHH Yields
To demonstrate the impact of microbioreactors, we conducted a DoE-based study on a Pichia pastoris strain producing a bivalent VHH. The study involved a full factorial design with 16 microbioreactor runs (4 factors, 2 levels), each run conducted in duplicate.
Results and Confirmation in Lab-Scale Bioreactors:
This study identified several parameter sets that significantly improved productivity, revealing key factor interactions. The optimized conditions were validated in lab-scale bioreactors, leading to a ~40% increase in VHH yield compared to standard cultivation conditions. These results underscore both the effectiveness of time and resource-saving microbioreactors in process optimization, and the strong transferability of findings to larger-scale systems.
Contact us to learn more about VALIDOGEN's strain development & process development programs.
Iskandar Dib, Principal Scientist and BD manager, iskandar.dib@validogen.com
Rosie Maddock, BD manager, rosie.maddock@validogen.com
