STREAMLINING FERMENTATION

The fermentation industry is not only labour but also energy intensive industries. Some of its products are facing intensive competition not only from the chemical industries producing the same products. In the case of certain fermentation products that could not be manufactured chemically this would not be a threat. The other threat is the competition from countries like China and India which could produce the same products but much cheaper

In order to survive any fermentation industries must be competitive enough to be able to produce fermentation products at a competitive price. One of the available methods to cut the cost of production thus lowering the final price of the products on the market is to be more efficient in its production. This would involve streamlining the fermentation industries in terms of improving efficiency of production, using less energy or using energy more efficiently

Streamlining could be referred as the improvement of an overall process, and the individual steps of the process, with a goal of meeting or exceeding client needs and expectations. The exercise of streamlining could itself be applied in many activities such as business, motorcar production, office management as well as fermentation industries

Stream lining is a rational exercise, whereby the whole fermentation process right from upstream to downstream is identified. The various steps involved are studied for room for improvement and whether they are run under optimal conditions. The success will be reflected in the end results that are expected. The company has shown much improvised financial performance in the last two years as a result of the financial as well as administrational restructuring that has been initiated during the period.

The fermentation industry is a dynamic entity that follows the sequence of events right up from upstream to downstream. It is often considered a one way flow. Any changes upstream in the streamlining process will affect the efficiency of the downstream unit processes. Care has to be taken to see that once streamlining process has been effectively carried out by not causing changes in operating regimes or even microbial contamination as the whole streamlining activity will be thrown out of gear. In the streamlining of the fermentation industries it is often a challenge to maintain this sensitive and optimal window of operations as the process is sensitive and fine tuned

IMPORTANT STEPS IN STREAM LINING

1 LOGISTICAL ARRANGEMENT OF UNIT OPERATIONS FOR SMOOTH TRANSFER SPATIALLY AND TEMPORALLY

The arrangement of the unit operations must be in logical sequence of the flow and must be within proximity of each other to allow smoother transfer between one process and another

2 SMOOTH VOLUMETRIC FLOWS FROM START TO END TO AVOID BOTTLENECKS

During the fermentation process there must smooth flow of materials being transformed right up from upstream, mid stream to downstream. The volumetric flows, materials and even man power must be considered

3 PROPER UNIT OPERATIONS ARE OPERATING EFFICIENTLY
The proper unit operations of the right capacity and specifications must be used. The equipments must be efficient and in good order and functioning properly. In certain situations there must be stand by units in case of emergency failures

4 FERMENTATION FLOW IS CLOSELY MONITORED BY SENSORS AND UNDER FULL CONTROL OF FEED BACK LOOPS

In this age of automation, sensors, computers and feedback loops will give us the immediate status of the process temporally as well spatially. This computer displays allow us to look graphically at the process and detect where likely trouble spots will occur or any build up of problems in the process



5 NEED OF SOPs
The use of SOPS will allow consistency of process, materials and products and avoid sudden problems occurring

6 NO ROOM FOR CHANGES
If in the application of streamlining is carried out, any sudden changes may affect the streamlining. Therefore it is important no sudden changes are carried out suddenly. In fermentation using non homogenous substrate composition this can be a challenge!





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BRINGING QUALITY CONTROL INTO FERMENTATION WORKSHOPS

In the last few years and up to the present, there seems to be many fermentation technology workshops being offered by the universities.
Analyses of the brochures and advertisements about the fermentation workshops offered have left many questions on:

1 Quality of the workshops
2 Course contents
3 Degree of hands on practicals offered to participants
4 Experience and qualifications of those conducting the fermentation
Workshops
5 Number of participants and work experience
6 Whether the so called “hands on” workshops are just demonstrations or “ look on” workshops
7 Whether those workshops involve real industrial or case solving workshops
8 Whether there are ‘brain storming sessions” with experienced facilitators

There should be some sort of accreditation and validation of these fermentation technology workshops, so that all parties concerned will benefit from the course. This continuous monitoring and assessing of the fermentation technology workshops will ultimately lead to better quality fermentation workshops.

COST OF WORKSHOPS
I don’t think the cost of attending the workshops will be an issue if real quality courses are being offered. Most companies are more than willing to pay if the courses are really positive and contributing to the company

REASON FOR ATTENDING WORKSHOPS
As I have noticed in many fermentation workshops, the workshop are supposed to be practical orientated. So stop wasting too much time in giving unnecessary lectures. After all most of the participants have enough experience or education. The reason they are attending the workshops are more to learn something new or upgrade their knowledge.

That is why I feel in such fermentation workshops, the participants should be more focused as the target group and not taking from such a diverse background

SYLLABUS OF WORKSHOPS

This is a very sensitive part of any fermentation workshops. I cannot help noticing almost all the fermentation technology have almost the same course contents, Very basic and very introductory. More the type the salesman would have demonstrated after you have bought the fermentors!

They teach you only the basics. Maybe for that syllabus its more suitable for those who really knew nothing about fermentors

Usually when we attend workshops we are trying to learn things which are not in the books or lecture notes. We are interested in real experience or tips and techniques

You need to have specific workshops and more in depth. For example, just one three day workshop covering aeration of fermentors, another three days for fermentor sterilization. Now that is really hands on workshops!!

Organizers of fermentation workshops should look towards making more advanced and diverse topics for their course. In reality there are demands for such fermentation workshops and its application in various fields

“HANDS ON”= DEMONSTRATIONS?
It is just illogical to say that the workshop is hands on when the participants are only exposed to one fermentor. It is not hands on workshop if the paricipants are really not involved in the practical but just observing the demonstrator


TIME ALLOCATION
I really have my doubts you can learn really much or significant within two or three days. And covering such diverse topics….


THE FACILITATORS

The track record of the facilitators must be impressive with respect to their academic and professional experience. Sad to say in most of these workshops not much is said about the identity of the speakers or their experience. There is often a void in the listing of their industrial experience

What I find so sad is the claims of how good they are just “self praise “comments within their own websites. With regard to how good you are or not is not for us to judge but by others or our peers!

In the end as I can see it, the success of the workshop is based more from the positive changes, acquiring of knowledge and experience and the change it can bring back to the company. Failure to achieve this would mean that the workshop is a failure and just a waste of time and money but a well paid holiday and getting a valueless paper certificate of attendance

It is for this reason that when holding the workshops, that reputation is at stake. If the reputation is bad its doubtful more participants will be coming to attend more workshops










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REHABILITATION OF PETALING JAYA LAKES- THE FERMENTATION TECHNOLOGY WAY

PICTURE TAKEN FROM ALLMALAYSIA INFO
INTRODUCTION
I just cannot help laughing at the futility of efforts in trying to rehabilitate the two recreational lakes serving the Petaling Jaya community. Historically, these lakes were originally formed during its hey days of tin mining activities. There were numerous tin mining lakes then in and around Petaling Jaya stretching from Sungai Besi to Sungai Way. The water quality of the lakes then was excellent. You can sense its cleanliness by just observing visually the clarity of its water

FUNCTION OF THE LAKES
These lakes which provided so much joy and happiness to residents and visitors alike has since then deteriorate in quality due to pollution due to rapid urbanization and city development.

There were concerns generated about the polluted status of the lahes which behaves more as wastewater receptacle rather than recreation lakes. Some of the news went even as far as declaring the lakes as being toxic and not capable of supporting healthy life forms such as fishes.

BASIC STUDIES
There were some basic scientific studies done on the lakes, mostly as field course or final year research projects. In most cases these studies are not comprehensive enough and with no clear objectives of trying to solve the problem of the lakes. Most of these studies are just simple wastewater characteristic studies involving few basic parameters or just taxonomic studies trying to identify the names of the algae or bacteria found in the lakes. In all these studies admittedly are very qualitative or semi quantitative to have significant input in solving the problems at hand

DATA AND SAMPLINGS
To make things worst some of these studies are more of “one off| studies without proper plan and research being done before the studies are taken. While it is true even sloppy work will still generate data, but how relevant or dependable are these data? Can these data be relied upon?

The data obtained and its validity or accuracy are determined by many factors. After all even a wrong sample can still yield data!!!
The validity of the data depends a lot on the sample and how sampling activities are carried out. At best the data obtained is just a snapshot in space and time and may be only valid for the sample in question. We cannot extrapolate on the state of the lakes based on this few poorly executed samples

Despite having the most advance sophisticated analytical instruments, the results would not be meaningful if sampling errors are done upstream

That is why I find ot so hilarious when there are water characteristic reports of the lake showed parameters such as dissolved oxygen achieving 9 mg/litre This is too good to be true!. Yet common sense and visual observations showed the lake to be much polluted with bubbling methane gas, foul smelling H2S and dead fishes floating.

If half hearted efforts are being made, we might as well don’t carry out any wastewater analyses. At least you save time, effort and money. To add insult to injury there are people who try to make far reaching conclusions and assumptions based on these flawed data.

Since scientific data such as the water characteristics are very important, proper sampling studies must be carried out. I often wonder if such data can withstand the challenge of environmental litigation in court?


FUTILE EFFORTS IN REHABILITATION
Just go to any doctor if you got medical problems. The doctor would not be able to find the proper cure unless he has done comprehensive clinical examinations on the patient. The same situation applies to the lake rehabilitation efforts. You cannot cure a sick lake by not finding the real cause of the problem.

Futile efforts were made to rehabilitate the lakes and huge sum of taxpayers money invested into the projects. However, from observations all those rehabilitation projects don’t seem to work.

Why do you ask that this topic be discussed in this fermentation technology blog? Well, the solution to this polluted lake could be solved if we try to understand the problem from the application and understanding of fermentation technology. After all, the lake is in itself a huge bioreactor or fermentor. Maybe there are lessons to be learnt from fermentation technology that will help understand the problem and how to solve it

THE LAKE AS A FERMENTOR
Maybe its due to my training or obsession with fermentation technology, but I seem to see almost everything in terms of the fermentor. The lake is one good example of a fermentor! So if the lake is polluted we can conclude it is one fermentation process that has failed or succinctly it is the bioreactor or fermentor operating regimes that failed. The question is which parameter is it?



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SPREADING THE WORD…! (BRINGING FERMENTATION TECHNOLOGY TO SCHOOLS AND UNIVERSITIES)

Judging from the number of visitors visiting this site, and the number of emails received, it is heartening to know that there are a lot of people out there who appreciate fermentation technology. Initially I was under the impression that the interest in fermentation are only shown by wine lovers who loved making and drinking their own wine. Well, I am glad I was wrong…….:)

Partially the success of this site is because the importance of fermentation technology as a biotechnology subject and also because of its huge industrial importance. This is judged by the popularity of certain fermentation articles in this blog.

As far as I know, fermentation technology is a subject though borne as far as the age of human civilization but its future will even be greater. It is very important therefore that the knowledge of fermentation technology should be feely available to all. Fermentation technology should not be regarded as the “lost ark” available to the very selected few.

In view of the importance of this subject concrete steps must be taken to spread and transfer the technology to everyone interested especially students in schools, colleges and universities. After all the future of fermentation technology will be in their hands. The teaching syllabus in schools and universities should incorporate the subject of fermentation technology as one of the integral subjects in their teaching

I do know that to carry out proper fermentation technology is a very heavy investment. But that does not mean that such subjects cannot be taught in schools. It is more of sharing the resources and expertise to bring the subject of fermentation technology to every school in the country. In this sense I must applaud the UK government and NCBE for coming together to create mobile teaching unit that can bring fermentation technology to schools at a minimal payment. Using this mobile teaching unit not only are they prepared with qualified speakers but also all the necessary laboratory equipment to carry and demonstrate fermentation technology

In this age of technology and specialization we do need specialists or experts to enlighten the students on the wonders of fermentation technology. By doing this, there will be the interests in pursuing fermentation technology and biotechnology among the public and students


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IMPORTANCE OF FERMENTOR DESIGN IN MINIMIZING ENERGY CONSUMPTION AND INCREASING YIELD

The main function of the fermentor tank is to hold the volume fermentation broth. In fact any vessels or container can be used to carry out the fermentation process. Fermentors differed from any container by allowing optimal fermentation process to occur through design and control

It is almost unbelievable that the concept of CSTR still dominates the day, years after its inception during penicillin fermentation. Only lately have attempts been made to come up with fermentors with novel or new designs.

The change towards new design fermentors is more to:
1 New fermentation products
2 Shift from high volume low value products to low volume and high value products

Any changes in the fermentor design must be with the purpose of improving the efficiency of the fermentation process in terms of yield and productivity or increasing its mass transfers and lowering energy consumption

In the old days it seems that almost any product fermentation is just forced into the CSTR. This was the mental block that hover over most engineers and fermentation technologists that one fermentor can be used for all types of fermentation!. It just doesn’t make sense!

Nowadays the design of the fermentor is more to accommodate the demands of the type of fermentation process. It seems in the past the engineers building or designing the fermentors are not able to think outside the box. The rigidity of their thinking is as rigid as the fermentor design

The fermentation process is considered complex with physical chemical and microbiological continually changing. With this in mind the design of fermentors must always be responsive. The fermentor design must not only be looked upon as fixed unit processes undergo by the fermentor such as standard stirrer specifications, aeration and even the sterilizing specifications. It is doubtful one standard design fermentor can bring out the best for a variety of fermentation carried out in the lifetime of the fermentor.

So, it is back to the drawing board in the design of the fermentors and a compulsory re education in fermentation technology for those involved in the design of fermentors. Reengineering and novel engineering is a must for the future of fermentors and fermentation.

The trouble with the design of fermentors in the past is that there is too much emphasis on engineering and math with poor understanding of the fermentation process. Sheets and sheets of the blueprint is the testimony to this

It is recommended that:

1 Understand the fermentation process first
2 Determine the rate limiting steps of the fermentation process
3 Understand the characteristics of the fermentation broth
4 Carry out feasibility lab studies before the design is accepted
5 Determine the flow and mixing pattern of the fermentor before determining the final optimal geometry
6 And other relevant studies

The key performance index in all the designs of the fermentors is cost. One of the major liabilities is energy. A fermentor is not a dead or innate structure metaphorically speaking. It consumes and even generates energy depending on the situation. Energy costs may not be a problem if you are dealing with small fermentors or working in government fermentation laboratories. But in industries, the energy costs could be very prohibitive and will add cost to the final fermentation products

If we analyse the energy consumption in a typical fermentor, most of the energy requirements are for:

1 Aeration
2 Stirring
3 Heating and cooling activities

Aeration is necessary in any aerobic fermentation process. The amount of aeration should reflect the oxygen demand of the fermentation process at that temporal and spatial status. What is important is that the aeration process should always be able to provide enough oxygen in the narrow window during the fermentation process. Providing more not only add up to the energy costs but might even complicate the fermentation process. Insufficient aeration might result in certain zones of the fermentor being deprived of oxygen and affect the fermentation process

In deciding the aeration requirements we have to consider many factors such as:
1 Type of aerators or spargers used
2 Location of spargers within the fermentors
3 Demand of oxygen as function of time of fermentation progress
4 Presence of mixers or stirrers in fermentors
5 Feed back loops to stirrer and aerator volumetric rate

Easier said than done. There is really no such thing of using the optimal aeration conditions of one fermentation process to be used on another. No two fermentations are the same. The optimal aeration conditions for fermentation have to be individually determined. This itself is the problem of having customized designed fermentor as it might only be suitable for one type of fermentation and not another

It is a known fact that experience in fermentation beats all the formal knowledge or information from books.

The choice of aerator is important and will decide whether the aeration costs will be higher or lower. It has been shown that aeration by air compression is only about 40% efficient in terms of electrical energy while agitation by turbine is about 90% efficient. Surprisingly in my experience as consultant on a trouble shooting job I have seen many clients are convinced by very qualified engineers who proposed air compression. Poor clients!

Use of sensors n feed back lops important. We need a reactive fermentor to detect changes and operate within narrow window of process optimization

Whole objective of stirring to homogenize or keep broth in suspension. How powerful we stir are often determined by the nature of the rheology of the fermentation broth. Mixing and aeration should be interplayed where a compromise is made between keeping the components of the broth in suspension yet still keeping the minimal amount of dissolved oxygen concentration enough to support the needs of the microorganisms. Excessive stirring may not only be demanding on the energy but also damaging to the microorganisms


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OXYGEN CONTROL AS FEED CONTROL IN FERMENTATION

I have always found the study of oxygen very interesting and complex, both at the level of microbial metabolism as well at the level of fermentors. The two levels of aeration and oxygen activity are connected by involving the same cultures. The differences in response to oxygen are more at the concentration of microorganisms involved and the scale of the effect.

In most fermentation studies, the supply of oxygen is looked upon more as a requisite of the process where oxygen is the terminal electron acceptors. Aeration has never been really exploited in the controlling of the fermentation process. In most cases just supply it continuously. Very rarely oxygen is seen from the point of view of controlling and manipulating the activity of the microorganisms. Maybe this is attributed to the poor understanding of the physiology of oxygen upon the metabolism of the microbes.

A lot of researches has been done on the effect of oxygen on the metabolism of the microbes. While in a way oxygen seems or is required by obligate aerobes and may even be lethal to obligate anaerobes, the effect is not clear cut.

In aerobic microorganisms .although oxygen is not lethal but in reality the aerobic microorganisms have a shield of enzymes such as catalase and superoxide dismutase which detoxify the oxygen. In the case of strict anaerobes the absence of such enzymes makes oxygen lethal

The point is simply oxygen is too reactive for comfort!

Even though aerobic microorganisms need oxygen due to the presence of the TCA cycle in their metabolism, there are part of the metabolic pathway which feeds to the TCA cycle as being anaerobic or fermentative. The success of these microorganisms depend on the smooth equilibrium which occur between the two types of pathways. Sudden changes to the smooth coupling between the aerobic and anaerobic part of the metabolic pathway could throw the physiology of these microorganisms out of gear

Many studies have shown that oscillatory or transient aeration of cultures could result in sudden changes in the metabolism leading to higher metabolic rate or even diversion of metabolism and formation of fermentation products. The bad news is that such transient aeration often result in the quick death of the microorganisms

The most crucial point in all these studies is the time lag after oxygen is manipulated and the ability of the microorganisms to respond. Quick alternations between the different phases of aeration tend to upset the physiology of the microorganisms

The point is studies need to be done if oxygen can be used to manipulate fermentation positively!

The most common manipulation of oxygen in industrial fermentation are:

1 Varying the supply of oxygen by controlling the stirrer speed
2 Varying the supply of oxygen with the demand of microbial growth in fermentors
3 Using pure oxygen or oxygen under increased pressure at certain stages of the fermentation process
4 Increasing the mass transfer rate of oxygen by using different size bubbles





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MICROBIAL GROWTH FORMS IN FERMENTOR.

Microorganisms in nature behave differently compared to when they are in laboratories or under fermentor conditions. In nature, microorganisms are generally not well off and are often occurring under the feast or famine environment. Their growth form is often affected by these conditions such as formation of spores and diffusive hyphal growth.

It is often said that for microorganisms living in the laboratories or fermentors, they are having a comfortable and luxurious life surrounded by rich nutrients and optimal environment. Their growth forms are therefore different compared to their microbial kins in nature. ( There are however microorganisms in the laboratory suffering cryogenic freezing…hehe)

In reality, those microorganisms living in the rich and optimal environment of the fermentors are in fact suffering and living under physiological stress. They are facing extreme over crowding and high density living being crammed within such limited volume. Their environment is often very viscous to their comfort. They face a lot of shearing forces especially those in the proximity of the shearing blades of the impellers. Exploding bubbles and hydrodynamic shearings attack them non stop for comfort. And physiologically they are forced to breed and multiply to fulfill their master’s wishes to produce more and more fermentation products till they die!

Under such stressful conditions their growth and growth forms are affected. One of the most common growth forms commonly encountered in fermentor growth are the formation of microbial granules or pellets. Granules in this context do not refer to the cytoplasmic inclusions but a form of microbial aggregate.

Despite the common occurrence of granulation in fermentors many are still are not aware of the causes of their formation. This is the result of dichotomy of approach and making quick conclusions from a few research observations.

Before we go further let us look at the nature of the microbial granule or aggregate.
Microbial granules are pellet like structures in which microorganisms are entrapped. These granules are basically EPS in nature and most times dense or compact. In terms of composition they are similar to microbial film thus indicating similar physiology and biochemistry of formation. Their unique morphology are more due to the strong and complex hydrodynamic conditions surrounding their environment. While the nature of microbial films is surface dependent, microbial granules are independent entities although they might have same origin or biogenesis

There are four important points to consider in the formation of granules:

1 The nature of microorganisms
2 Its physiology
3 Nutrient environment
4 Hydrodynamic condition of fermentation broth

In microbial granulation mostly involve bacteria. In a way it does not reflect that fungi can’t form granules as fungi are known to be important component in floc formation. It is most attributed to fungi unable to live in anaerobic conditions or that they are easily broken up by the hydrodynamic forces. Fungi are also not really EPS producers.

The fact that higher amount of microbial granules are associated with anaerobic reactors do say a lot about how they are formed. You cannot say that there are a lot of competition in the anaerobic environment as only few anaerobic bacteria succeeds in establishing themselves there. There is higher number and diversity of microorganisms in microbial flocs than in anaerobic granules

The formation of EPS is a physiological response to stress. During stress the first reaction of microorganisms is self preservation. Although it is seen the formation of EPS is a waste of carbon, energy and protein, it must confer advantages to the producers. Living in the fermentor is stressful as said earlier. While the EPS is seen as a shield or barrier to protect the organism, it is in itself a barrier to diffusion of nutrients

The strong hydrodynamic conditions not only shear cells but it also help in the pelletization process itself. The forces help in forming rounding and compacting the granules. The steady state size of the granules reflect the point of stability of the structure undr the existing operating conditions.

I cannot really see how the microorganisms in the pellet enhanced the bioprocess as the tight granules hinder the diffusion or mass transfer of nutrients. I do agree that it helps in the settlement and clarification of the wastewater treatment.



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RAPID FERMENTATION

One of the indicators of an efficient fermentation process is the shortest or optimal time it takes to complete the fermentation process. In fermentation industries or any other industries TIME is MONEY!.

Longer fermentation time means:

1 More power or energy for aeration or stirring
2 More time to utilize the fermentors again for more production
3 Labour cost saved

So there is always the attempt to shorten the fermentation time. Shortening of the fermentation time could be achieved by:

1 Increasing the concentration of biomass of microorganisms in fermentor
2 Optimizing the fermentation conditions in terms of mass transfers and nutrient and environment
3 Using high producing strains

In all, it’s more about looking at the various rate limiting steps and improving the step.

However, in trying to achieve rapid fermentation in terms of time, it is of utmost importance that the quality of the fermentation products itself is not affected. It is important too that the rapid fermentation steps would not create secondary problems both mid stream and down stream

In most cases fermentation is a complex process dictated by the physiology and metabolism of the microorganisms. The changes in metabolism will ultimately be reflected in the quality and composition of the fermentation products. You may achieve shortened fermentation time but is the quality of fermentation products compromised?

A good example is found in soy sauce and wine fermentation. It is not so much about the alcohol content to dictate the success of the fermentation process within the shortest time but the bouquet quality of the wine or soy sauce. You simply have to admit it best fermentation products are obtained by allowing it time to mature. The Japanese in the rush to make rapid fermentation often use high rate fermentation or employ enzyme hydrolyses in the early stage of fermentation, but the taste is not the same. The soy sauce tastes salty and looks dark but it lack the aroma flavour and taste

It just proves that the perfect fermentation is like a well orchestrated process. You must not hasten it without thinking the consequences

There is more in preparing the inocula or koji by just putting the necessary microorganisms. Fermentation is often complex and the proper succession of microorganisms is important. Any changes of conditions of the fermentation process will upset the normal or natural fermentation!

Raising the temperature to hasten the fermentation process is the most common technique. But at the same time increasing the temperature will destabilize the fermentation process. This is as shown in high rate anaerobic digestion process where even though biodegradability is enhanced, the VFA composition is changed and the process destabilized






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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!




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