Real-time monitoring and control of microbial bioprocesses with focus on the specific growth rate: current state and perspectives

Abstract

Understanding the growth characteristics of microorganisms is an essential step in bioprocessing, not only because product formation may be growth-associated but also because they might influence cell physiology and thereby product quality. The specific growth rate, a key variable of many bioprocesses, cannot be measured directly and relies on the estimation through other measurable variables such as biomass, substrate, or product concentrations. Techniques for real-time estimation of the specific growth rate in microbial fed-batch cultures are discussed in the present paper. The advantages and limitations of different models and various monitoring techniques are discussed, highlighting the importance of the specific growth rate in the development of fast, reliable, and robust processes for the production of high-value products such as recombinant proteins.

Real-time estimation of biomass and specific growth rate in physiologically variable recombinant fed-batch processes

“…Specific rates such as the specific growth rate are especially important process variables, acting as a descriptor of the physiological state, with impact on biomass production, product quantity, and product quality [43]. Furthermore, if a system is fully quantified, a great deal of understanding is achieved that can be easily communicated.…”

Microcalorimetric assays for measuring cell growth and metabolic activity: Methodology and applications

“…In addition to research purposes, monitoring cell growth, and particularly microbial growth, is crucial in many industrial processes such as food production or biomedical applications [4,5]. In many cases, monitoring the increase of the cell population is sufficient to assess the effect of a defined parameter (the efficacy of a new drug, or the effect of a toxic compound for example [6]).…”

Maximizing biomass concentration in baker’s yeast process by using a decoupled geometric controller for substrate and dissolved oxygen

“…With the advancement in monitoring techniques, researchers have explored the application of dielectric spectroscopy and calorimetry (Schuler and Marison, 2012;Biener et al, 2012) to control the feed rate of the substrate in small-scale bioreactors. However, these tools thus far remain untested in an industrial environment.…”