Leveraging Fermentation Heat Transfer Data to Better Understand Metabolic Activity - - BioPharm International

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Leveraging Fermentation Heat Transfer Data to Better Understand Metabolic Activity


BioPharm International
Volume 21, Issue 4

ABSTRACT

Tracking the heat removal data from fermentation processes is a powerful aid in specifying scale-up characteristics such as cooling requirements. These same data can help define the metabolic activity of the cells in the fermenter. By reversing metabolic heat equations and defining the heat characteristics of the fermenter, the oxygen uptake rate can be determined from the fermenter heat removal data. This offers a simple, inexpensive method to determine the metabolic state of the fermentation. When the heat input and removal for a fermentation process have been properly investigated, the oxygen uptake rate determined from the metabolic heat equation will closely follow the values measured with external devices such as a mass spectrometer.

Gaining an understanding of a fermentation process can take many forms, such as investigating biomass increase, substrate use, metabolite production, and oxygen use. Of these metabolic indicators, one of the most common is the analysis of oxygen use. The oxygen uptake rate (OUR) can be measured through multiple methods. These techniques include a dynamic OUR determination method and a steady-state OUR method based on an overall oxygen balance. The dynamic OUR determination uses a dissolved oxygen probe that is located in the fermenter. The airflow is temporarily stopped during the fermentation and the rate of dissolved oxygen (DO) decline is used to determine the use of oxygen by the cells. This method requires accurate determination of the mass transfer coefficient and assurance that the system is not in the regime of DO dependent oxygen transfer. This method can be further confounded by factors such as slow DO probe response and localized oxygen conditions near the probe.

The steady-state method for determining OUR uses a material balance to calculate the amount of oxygen that is consumed by the fermentation. Essentially, the amount of oxygen entering the system is subtracted from the amount of oxygen leaving the system, and that difference is the oxygen uptake. This method requires very accurate gas flow measurement, a nitrogen balance to correct for flow differentials, and analytical equipment, such as a mass spectrometer. When all of the components are working properly, this method is quite accurate in describing the OUR of the entire system. Another method to determine OUR relies on a correlation between the fermentation heat transfer rate and oxygen uptake rate based on theoretical and empirical data. This method is very practical and can provide a quick answer because it uses equipment that is generally in place for a fermenter.

BACKGROUND

Heat balances often used in chemical engineering to break down very complex systems into manageable pieces. The underlying principle is that the heat inputs and outputs can be summed for a system to determine the flow of heat. In the case of fermentation, the heat balance represents a biological system that is in steady state. This means that the net heat difference when the inputs and outputs are added together is zero. Heat is generated and lost in fermentation systems. If the heat generation exceeds the heat loss, then the fermentation will require cooling to maintain steady-state conditions or steady temperature for the heat balance.

Sources of heat for fermentations include feeds, air in-flow, agitation, recirculation pumps, and the metabolic activity of the cells, which is the largest heat generation component. Sources of cooling for fermentations may include water evaporation, environment, and broth temperature increases. Each of these heat balance components is described in the following sections.


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