implementation as well as any other monitoring and control strategy depends on: (1) the availability of robust, reliable, low-cost, easy-to-use online/at-line sensors; (2) a complete understanding of the variability inherent in the bioprocess and introduced by the raw materials; and (3) the availability of sufficient time to develop a process that is amenable to the application of any online monitoring or control procedure during manufacturing [5]. However, it may be difficult to implement monitoring and control strategies because they require the use of experimental design tools, which for some industries such as biopharmaceuticals implies a high-cost, time-consuming procedure.On the other hand, several studies showed the advantages of developing mathematical models for the design, optimization, and bioprocess control. However, the vast majority of industrial processes are still controlled and optimized without the explicit use of these models. Nevertheless, the development of mathematical models that can describe bioprocesses has become essential because it is usually cheaper to model a system and simulate its operating conditions than to perform laboratory experiments. In some cases, apart from the economic point of view, there are other practical reasons, such as safety and ethical questions that make experimentation impracticable in real systems [6,7].Mathematical modeling, monitoring, and the real-time control of bioprocesses is a major challenge for biotechnologists and control engineers, leaving them the task of creating communication platforms among themselves and the industry so that the novel techniques that are developed can be used on an industrial level.The development of modeling strategies, real-time monitoring, control, and optimization is necessary to guarantee operational reproducibility, quality control, and run-torun consistency for both developmental and scale-up purposes [8].However, the significant uncertainty of the models' structure and parameters, and the nonlinear and dynamic nature of these systems make bioprocesses modeling, monitoring, and control a difficult and challenging task. Also, implementation of the most suitable type of automated analysis is a main difficulty.Automated analysis can be performed in two ways: by using a measurement probe inside the reactor, avoiding the need for sampling; or by automated sampling and subsequent sample analysis. The main drawback to the first approach is the scarcity or even lack of inexpensive and robust probes able to allow direct and in-line measurements of state variables. For the latter, expensive, time-consuming, and mostly offline methodologies (e.g., chromatography, electrophoresis, and mass spectrometry) are usually applied that required highly skilled technicians. Nevertheless, although it is rarely available, timely process information about fermentation biomass, substrates, intermediates, products, and nutrients is required to make effective control decisions [9,10]. For instance, in a bioprocess it is crucial to keep cells alive ...