Abstract
The development of autonomous agents in bioprocess development is crucial for advancing biopharma innovation. Time and resources required to develop and transfer a process for clinical material generation can be significantly decreased. While robotics and machine learning have greatly accelerated drug discovery and initial screening, the later stages of development have primarily benefited from experimental automation, lacking advanced computational tools for experimental planning and execution. For example, in the development of new monoclonal antibodies, the search for optimal upstream conditions (such as feeding strategy, pH, temperature, and media composition) is often conducted using sophisticated high-throughput (HT) mini-bioreactor systems, while the integration of machine learning tools for experimental design and operation in these systems have not matured accordingly. In this work, we developed an integrated user-friendly software framework that combines a Bayesian experimental design (BED) algorithm and a cognitive digital twin of the cultivation system. This framework is digitally linked to an advanced 24-parallel mini-bioreactor perfusion platform. This results in an autonomous experimental machine capable of: (1) embedding existing process knowledge, (2) learning during experimentation, (3) utilizing information from similar processes, (4) predicting future events, and (5) autonomously operating the parallel bioreactors to achieve challenging objectives. As proof of concept, we present experimental results from a 27 day-long cultivation including 20-days operated by the autonomous software agent, which successfully achieved challenging goals such as increasing the viable cell volume (VCV) and maximizing the viability throughout the experiment.