Automated Bioprocess Feedback Operation in a High-Throughput Facility via the Integration of a Mobile Robotic Lab Assistant

Abstract

The development of biotechnological processes is challenging due to the diversity of process parameters. For efficient upstream development, parallel cultivation systems have proven to reduce costs and associated timelines successfully while offering excellent process control. However, the degree of automation of such small-scale systems is comparatively low, and necessary sample analysis requires manual steps. Although the subsequent analysis can be performed in a high-throughput manner, the integration of analytical devices remains challenging, especially when cultivation and analysis laboratories are spatially separated. Mobile robots offer a potential solution, but their implementation in research laboratories is not widely adopted. Our approach demonstrates the integration of a small-scale cultivation system into a liquid handling station for an automated cultivation and sample procedure. The samples are transported via a mobile robotic lab assistant and subsequently analyzed by a high-throughput analyzer. The process data are stored in a centralized database. The mobile robotic workflow guarantees a flexible solution for device integration and facilitates automation. Restrictions regarding spatial separation of devices are circumvented, enabling a modular platform throughout different laboratories. The presented cultivation platform is evaluated on the basis of industrially relevant E. coli BW25113 high cell density fed-batch cultivation. The necessary magnesium addition for reaching high cell densities in mineral salt medium is automated via a feedback operation loop between the analysis station located in the adjacent room and the cultivation system. The modular design demonstrates new opportunities for advanced control options and the suitability of the platform for accelerating bioprocess development. This study lays the foundation for a fully integrated facility, where the physical connection of laboratory equipment is achieved through the successful use of a mobile robotic lab assistant, and different cultivation scales can be coupled through the common data infrastructure.