scale up fermentation

How to Scale Up Fermentation Processes

How to Scale Up Fermentation Processes: Considerations and Criteria

Fermentation is a bioprocess that involves the growth of microorganisms, such as bacteria, yeast, or fungi, in a liquid medium to produce various products, such as biopharmaceuticals, food and food additives, chemicals, and biofuels. Fermentation can be performed in different types of vessels, such as shake flasks, cell culture dishes, T-flasks, bioreactors, or fermenters.

scale up fermentation

Scaling up fermentation processes is the process of transferring a fermentation process from a small-scale laboratory setting to a large-scale industrial setting, with the aim of achieving the same productivity and quality of the product at a larger volume and lower cost. Scaling up fermentation processes is a challenging and complex task that requires careful planning and execution. There are several factors and parameters that need to be considered and controlled during scaling up fermentation processes, such as:

  • Cell expansion and density: The growth rate and biomass concentration of the microorganisms affect the product yield and quality, as well as the mass and heat transfer, nutrient delivery, and oxygen demand in the fermentation vessel. The cell expansion and density should be maintained at optimal levels throughout the fermentation process, regardless of the scale.
  • Mass and heat transfer: The transfer of mass (such as nutrients, oxygen, carbon dioxide, products, etc.) and heat between the liquid medium and the microorganisms is essential for the metabolic activity and product formation of the microorganisms. The mass and heat transfer rates depend on the physical properties of the medium (such as viscosity, density, etc.), the geometry and size of the vessel, the agitation speed and type of impeller, the aeration rate and type of sparger, etc. The mass and heat transfer rates should be sufficient to meet the demand of the microorganisms and to prevent accumulation of toxic metabolites or excess heat in the vessel.
  • Mixing: The mixing of the liquid medium and the microorganisms is important for achieving uniform distribution of temperature, pH, dissolved oxygen, nutrients, products, etc. in the vessel. The mixing also affects the shear stress and bubble size in the vessel, which can influence the viability and productivity of the microorganisms. The mixing intensity and efficiency depend on the agitation speed and type of impeller, the geometry and size of the vessel, the baffles or other devices that prevent vortex formation, etc. The mixing should be adequate to ensure homogeneity and stability of the culture without causing damage or stress to the microorganisms.
  • Gassing: The gassing of the liquid medium with air or other gases (such as oxygen, nitrogen, carbon dioxide, etc.) is necessary for providing oxygen for aerobic microorganisms or for controlling pH or redox potential for anaerobic microorganisms. The gassing also affects the mass transfer rate of oxygen and carbon dioxide in the vessel. The gassing rate and efficiency depend on the aeration rate and type of sparger, the agitation speed and type of impeller, the geometry and size of the vessel, etc. The gassing should be sufficient to satisfy the oxygen demand or pH or redox potential of the microorganisms without causing excessive foaming or gas holdup in the vessel.
  • Nutrient delivery: The delivery of nutrients (such as sugars, nitrogen sources, vitamins, minerals, etc.) to the microorganisms is essential for their growth and product formation. The nutrient delivery rate and mode depend on the type of fermentation configuration (such as batch, fed-batch, or continuous mode), the type of nutrient feed (such as concentrated solution, powder, or pellet), the type of feed pump (such as peristaltic pump, syringe pump, or piston pump), the location of feed inlet (such as top, bottom, or side), etc. The nutrient delivery should be controlled to provide adequate and balanced supply of nutrients to the microorganisms without causing substrate inhibition or accumulation of by-products in the vessel.

How to Choose Scaling Up Criteria?

The choice of scaling up criteria is a critical step in scaling up fermentation processes. Scaling up criteria are parameters or variables that are kept constant or proportional between different scales of fermentation vessels. Scaling up criteria are used to ensure similarity or equivalence of performance and behavior of the microorganisms and their products at different scales.

There are different methods or approaches for choosing scaling up criteria for fermentation processes, such as:

  • Keeping mixing times equal: This method assumes that mixing time is a key factor that affects mass transfer, heat transfer, and mixing homogeneity in the fermentation vessel. Mixing time is defined as the time required for a tracer substance to be uniformly distributed throughout the vessel by the action of agitation and aeration. Mixing time can be measured by adding a dye or an electrical pulse to the vessel and monitoring its concentration or voltage at different locations in the vessel. By keeping mixing times equal between different scales of fermentation vessels, it is expected that the mass transfer, heat transfer, and mixing homogeneity will be similar as well.
  • Keeping power to liquid volume ratio equal: This method assumes that power to liquid volume ratio is a key factor that affects mass transfer, heat transfer, and mixing intensity in the fermentation vessel. Power to liquid volume ratio is defined as the ratio of the power input by the impeller and the sparger to the liquid volume in the vessel. Power to liquid volume ratio can be calculated by measuring the torque and the rotational speed of the impeller and the pressure and the flow rate of the sparger. By keeping power to liquid volume ratio equal between different scales of fermentation vessels, it is expected that the mass transfer, heat transfer, and mixing intensity will be similar as well.
  • Keeping oxygen transfer coefficient or oxygen uptake rate equal: This method assumes that oxygen transfer coefficient or oxygen uptake rate is a key factor that affects oxygen availability and demand for aerobic microorganisms in the fermentation vessel. Oxygen transfer coefficient is defined as the rate of oxygen transfer from the gas phase to the liquid phase per unit driving force (such as oxygen concentration difference or partial pressure difference) in the vessel. Oxygen uptake rate is defined as the rate of oxygen consumption by the microorganisms per unit biomass in the vessel. Oxygen transfer coefficient and oxygen uptake rate can be measured by using dynamic or steady state methods, such as gassing out, sulfite oxidation, respirometry, etc. By keeping oxygen transfer coefficient or oxygen uptake rate equal between different scales of fermentation vessels, it is expected that the oxygen availability and demand will be similar as well.

Conclusion

Scaling up fermentation processes is a complex and challenging task that requires careful consideration and control of various factors and parameters that affect the performance and behavior of the microorganisms and their products at different scales. There are different methods or approaches for choosing scaling up criteria for fermentation processes, such as keeping mixing times equal, keeping power to liquid volume ratio equal, or keeping oxygen transfer coefficient or oxygen uptake rate equal. Understanding these methods and their advantages and disadvantages can help you choose the best scaling up criteria for your fermentation process, and accordingly the best fermentation equipment and stainless steel tanks.