SIZE DOES MATTERS!* * where fermentors are concerned

Size does matters in fermentation technology. Yet it is a topic which most people avoid talking about. Just try googling up the words “ size fermenters”. You don’t really get much information.

Size in fermentation technology affects everything right up from the initial of deciding to buy your fermentor to the final stage of downstream processing such as:

1 The choice of fermentors you want to buy or use
2 The fermentation process itself
3 Economics of production


BUYING THE FERMENTOR

In most cases, the fermentors sold by fermentor manufacturer come in certain range of sizes. These fermentor models are usually delivered at certain volumes or capacities. This is pure economics. By mass producing certain range they are able to keep the price down.
You simply just have to make your choice from the catalogue. You just might end up buying “over sized” or “under sized” fermentors.

I can see why fermentation industries or pilot plants go for certain large sizes fermentors. The bigger the fermentor the higher the capacity or the volume of fermentation products it can ferment. This automatically would result in lower cost for each unit fermentation product produced

As for pilot fermentation plants the requirements are different. Their sole purpose is to generate enough data from which an industrial fermentation process could be rationally estimated. In pilot fermentation plants they need to have a range of sizes leading from small laboratory scale to pilot scale fermenters. However the choice of sizes is judicious to ensure proper scale up rules are followed. Usually the jump in the size of the fermentors is not arithmetical but by magnitude power, at least by power of 10.



Irrespective of what the large size would be for pilot or industrial level requirements one need to know first the impact of increasing size on every aspects of the fermentation. The effects of increasing the size of fermentors will affect various parameters such as:

1 Design of fermentor
2 Materials to build the fermentors
3 Mass transfer processes
4 Effect on the physiology of the microorganisms
5 Complexity of aeration
6 Sterilization and cooling of fermentors
7 Minimal volume of broth needed


EFFECT OF HEAT MASS TRANSFER

It is often a misnomer to regard that the superiority of fermentation process over chemical process in its ambient or non harsh environment needed for the process. This reasoning is due to the involvement of various enzymes to catalyze the fermentation reactions.

What is often not appreciated is that while the fermentation process itself does not require high heat or harsh environment, it does depend a lot on heat for sterilization and for cooling of fermentors. This all add up to the final cost of the products.

In physics the transfer of heat can either occur through convection, radiation and conduction. In the case of fermentation processes, heat transfers are mainly by conduction. Heat is transferred through conductor such as the materials of the fermentor. The efficiency of this heat transfer are dictated by the nature of the conductor, thickness of the conductor and the ratio of surface area to volume of the conductor.

This would not be a problem for small fermentors such as the laboratory scale fermentors which maintained high surface area to volume ratio for easier heat conduction. In large size fermentors such as those found in pilot plants or industrial scale fermentors this could be a problem.
In efficient heat transfers could result in poor sterilization process or even leading to denaturation of broth and under sterilization of the media.

During sterilization the involvement of the heat could be seen in the rapid rise in temperature needed for sterilization and also the rapid cooling of the fermentation broth after the cooling. These factors need to be considered



EFFECT OF HYDROSTATIC PRESSURE

We all know the inner pressure of an operating fermentor is at least about 2 bars higher than the ambient pressure. Fermentation process are generally carried out in a positive pressure mode. However, this pressure we are referring to is indicative of the combined gas pressure acting especially in the gas space and the outlet valve of the fermentor.

What is often not appreciated is the liquid pressure exerted by the liquid column within the fermentor. The pressure of the liquid column is similar to the pressure exerted as we go diving into the depths of the ocean. The height of the liquid column and the density of the broth will influence the value of the pressure.

This hydrostatic pressure will not be a problem for small laboratory scale fermentor. It will be a problem for huge and tall fermentors such as those found in factories and even pilot scale fermentors.

The effect of such hydrostatic pressure will be seen clearly on:
1 The solubility of gases such as carbon dioxide and oxygen
2 On the metabolism of the fermentative microorganisms at the bottom of the tank

In aerobic fermentation more energy and more costs will be incurred in trying to pump the gas from the bottom of the fermentor.

Gas bubbles arising from the bottom of the fermentor will find it more difficult to expand and rise in overcoming the hydrostatic pressure. The size of the bubbles will be small and the bubble residence time will be longer compared to those in small fermentor.

If the fermentation products of the microorganisms are gases, then the back pressure will be created making it more difficult for the gas to diffuse out of the microorganisms. I is known that the presence of high hydrogen may result in the efficiency of the NADH2 dissociation which is crucial in the fermentation metabolism

Under certain situation such high pressure may even divert the pathway of the fermentation leading to lower yield of the desired product or formation of unwanted side products


INEFFICIENCY OF MIXING

Generally there is no problem in mixing using small size fermentors such as laboratory scale fermentors. Even without impellers the presence of aeration or sparger is enough to generate sufficient mixing.

It is different however when dealing with large fermentors. It is difficult to get complete or efficient mixings. This is one of the problems in scaling up studies in fermentors,

Over coming this inefficiency of mixings are usually solved through the combination of properly designed impellers to its operating regimes. This can only be achieved by doing preliminary studies on the fermentation characteristics and determining it on small scale studies in the laboratory

It is bad practice to straight away jumping into the fermentation process using standard data as each fermentation is unique.





EFFECT OF VARYING THE WORKING VOLUME

It is not an easy matter to just decide on what your working volume will be. There are many criteria to be determined in fixing your working volume. It is a well known fact changes in working volume will affect the surface area to volume ratio of the broth. Such changes would affect a lot of physical processes and mass transfers that lead to loss of water, viscosity, sterilization, oxygen transfer and the fermentation process itself.

In pilot plant, the choice of sizes of fermentors becomes even more crucial. Pilot plant should not be confused with contract manufacturing facilities. If pilot plants are used as contract manufacturing facilities the requirements are different. This has been recently discussed in this blog.

One of the pilot plant main activities is researching on the effect of scaling up before confidently saying that its ok to go ahead with industrial scale production. There are many problems confronting the whole process of scaling up. Data obtained must be reliable enough to give the confidence that everything will be fine during industrial production level


Various considerations are to be taken in choosing the right size as it affect various stages of the fermentation process. Of course it is very impressive to visitors if you show them you got the biggest fermenters (or white elephants) in your lab. Of course the bigger the fermenter is the more costly it is priced but when considering the economy of scale it actually becomes cheaper to produce fermentation products. In economics, where the average cost of production, and therefore the unit cost, decreases as output increases. The high capital costs of machinery or a factory are spread across a greater number of units as more are produced. It is generally cheaper to buy one big fermenter than a number of small fermenters giving the same total volume capacity

In terms of support services if you use a small laboratory scale fermenters you can use the existing general microbiology laboratory such as the autoclaves and other services. For large fermenters you need to acquire extra supporting services that could support the large fermenter. This of course is the hidden side of costing and investments

The rule is simple. Bigger size usually means more wastage of media power to sterilize etc. It does not mean simply bigger size would yield significantly more accurate data!




Type rest of the post here.