Applications of Digital Twins in Biological Industries: An Overview with a Case Study on Fed-Batch Monitoring of Pichia Pastoris Fermentation

Digital Twins (DTs) are digital representations of physical assets. DTs have emerged as a revolutionary concept in the field of biomanufacturing, offering virtual replicas of physical systems that enable comprehensive monitoring, analysis, and optimization of biological processes. This research provides an in-depth exploration of DTs in biomanufacturing, discussing their key components, modeling approaches, and applications. The importance of Process Analytical Technology (PAT) and sensor technology in DTs is emphasized, along with their role in real-time data acquisition and monitoring. To highlight the practical implementation and benefits of DTs, in a case study, a DT is developed for a fed-batch fermentor that produces Pichia pastoris. By adding unknown uncertainties to the fermentation process, the excellent performance of the developed DT is evaluated based on four states, namely biomass, glycerol, methanol, and protein concentration.