An Industrial Perspective on Scale-Down Challenges Using Miniaturized Bioreactors

Miniaturized stirred bioreactors (MSBRs) are gaining popularity as a cost-effective approach to scale-down experimentation. However, realizing conditions that reflect the large-scale process accurately can be challenging. This article highlights common challenges of using MSBRs for scale-down. The fundamental difference between oxygen mass transfer coefficient (kLa) and oxygen transfer rate scaling is addressed and the difficulty of achieving turbulent flow and industrially relevant tip speeds is described. More practical challenges of using MSBR systems for scale-down are also discussed, including the risk of vortex formation, changed volume dynamics, and wall growth. By highlighting these challenges, the article aims to create more awareness of these difficulties and to contribute to improved design of scale-down experiments. Miniaturized stirred bioreactors (MSBRs) are becoming increasingly popular in the biotechnology industry as a tool for rapid and cost-effective process development. Because of the small volume of MSBRs, there is an extreme scaling factor (>105) between these systems and the industrial scale process. This makes it challenging to establish industrially relevant conditions in the MSBR. There is usually a lot of focus on keeping one scaling parameter constant across scale. The challenge of keeping other relevant parameters constant simultaneously, or the potential impact of their deviating values on process performance, are rarely addressed. Thorough characterization and validation of MSBR results is important to confirm results found in smaller scale.