Rising demands for biopharmaceuticals and the need to reduce manufacturing costs increase the pressure to develop productive and efficient bioprocesses. Among others, a major hurdle during process development and optimization studies is the huge experimental effort in conventional design of experiments (DoE) methods. As being an explorative approach, DoE requires extensive expert knowledge about the investigated factors and their boundary values and often leads to multiple rounds of time-consuming and costly experiments. The combination of DoE with a virtual representation of the bioprocess, called digital twin, in model-assisted DoE (mDoE) can be used as an alternative to decrease the number of experiments significantly. mDoE enables a knowledge-driven bioprocess development including the definition of a mathematical process model in the early development stages. In this chapter, digital twins and their role in mDoE are discussed. First, statistical DoE methods are introduced as the basis of mDoE. Second, the combination of a mathematical process model and DoE into mDoE is examined. This includes mathematical model structures and a selection scheme for the choice of DoE designs. Finally, the application of mDoE is discussed in a case study for the medium optimization in an antibody-producing Chinese hamster ovary cell culture process.

This chapter summarizes in the beginning our current understanding of extracellular electron transport processes in organisms belonging to the genera Shewanella and Geobacter. Organisms belonging to these genera developed strategies to transport respiratory electrons to the cell surface that are defined by modules of which some seem to be rather unique for one or the other genus while others are similar. We use this overview regarding our current knowledge of extracellular electron transfer to explain the physiological interaction of microorganisms in direct interspecies electron transfer, a process in which one organism basically comprises the electron acceptor for another microbe and that depends also on extended electron transport chains. This analysis of mechanisms for the transport of respiratory electrons to insoluble electron acceptors ends with an overview of questions that remain so far unanswered. Moreover, we use the description of the biochemistry of extracellular electron transport to explain the fundamentals of biosensors based on this process and give an overview regarding their status of development and applicability.