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Industrial Scale Fermentation

In this industrial scale fermentation post we have briefly explained about basic design, media used in the industrial fermentation process, large scale production, upstream processing, industrial fermentation process, and downstream processing.

Industrial Scale Fermentation

A fermenter’s primary purpose is to provide an environment in which an organism may efficiently manufacture a desired product. The majority of them are made to keep high biomass concentrations, which are necessary for various fermentation processes.

Fermenter design, construction quality, mode of operation, and sophistication are all influenced by the production organism, optimal operating circumstances for target product formation, product value, and production scale.

The performance of every fermenter is determined by a variety of factors, but agitation rate, oxygen transfer, pH, temperature, and foam generation are critical physical and chemical characteristics that must be managed.

Basic Design

The materials used for construction of fermenter withstand repeated steam sterilization and are nontoxic. The reaction vessel is designed to withstand vacuum or else it may collapse while cooling. The internal surface is smooth and corrosion resistant. Either stainless steel or glass is used for construction.

It is surrounded by a jacket and sparger at the bottom through which air is introduced. The agitator shaft is connected to a motor at the bottom. It has ports for pH, temperature, dissolved Oxygen sensors for regulation.

Antifoam agents like animal vegetable oil, lard oil, corn oil and soya bean oil are used to control the foam. Modern fermentors are usually integrated with computers for efficient process monitoring and data acquisition.


Industrial Fermentation Process: Design of a fermenter

Media Used in Industrial Fermentation Process

Fermentation Medium

Although certain solid-substrate fermentations are carried out, most fermentation requires liquid media, commonly referred to as broth. Fermentation media must meet all of the microorganism’s nutritional requirements as well as the process’ technical goals.

Some media also include animal fats and plant oils, which are commonly used as supplements to the main carbon source. The following properties should be present in any medium used for large-scale production.

It should be cheap and easily available. It should maximize the growth of the microorganism productivity. It should minimize the formation of undesired products. It should include carbon, nitrogen, energy, and micronutrients that are essential for industrial fermentation process.

Molasses, lignocellulosic waste, and corn steep liquor are examples of waste products from various industrial fermentation process that are commonly utilised as substrates for industrial fermentation process. Other components utilised in industrial fermentation process include minerals, vitamins, and growth agents, in addition to carbon and nitrogen sources.


Industrial Fermentation Process: Components of Fermenter


Normally, sufficient quantities of cobalt, copper, iron, manganese, molybdenum, and zinc are present in the water supplies, and as impurities in other media ingredients. For example, corn steep liquor contains a wide range of minerals that will usually satisfy the minor and trace mineral needs.

Growth factors

Many bacteria can make all of the vitamins they need from simple components. Other bacteria, filamentous fungus, and yeasts must be added to the fermentation medium as supplements. As tiny pollutants, most natural carbon and nitrogen sources also contain at least some of the essential vitamins. Amino acids, nucleotides, fatty acids, and sterols, among other essential growth factors, are provided either in pure form or as less expensive plant and animal extracts for cost reasons.


Some fermentation requires the addition of specific precursors, most notably for the formation of secondary metabolites. When they’re needed, they’re usually added in little amounts and in a pretty pure form. In the manufacture of penicillin, side chain precursors such as phenyl acetic acid or phenylacetamide are used.

Large Scale Production

Industrial fermentation process involved in biochemistry, genetics, molecular biology, chemistry, chemical engineering and process engineering, mathematics, and computer technology are just a few of the fields that contribute significantly to the creation of a fermentation process and fermentors. Upstream processing (USP) and downstream processing (DSP) are both stages of a typical procedure.

Upstream Processing

It is the initial step in the fermentation process, during which biomolecules such as bacteria or other organisms are cultivated in a fermentors. Inoculation development, scale-up, medium preparation and sterilisation of media, as well as the fermentation process, are all part of upstream processing.

Inoculum development

It’s the process of transforming a population of microorganisms from a dormant stock culture into a state suitable for inoculating final production fermentors.

It’s an important step in the fermentation process. It’s a step-by-step procedure that uses increasing amounts of media. Inoculum media are often designed to promote rapid cell proliferation rather than product production.

Inoculum scale up

It is the seed culture preparations in sufficient quantities to be used in the bigger fermenter vessel. It entails growing the microorganisms from the pure stock culture in many fermenters in a row.

By doing so, the time it takes for bacteria to grow in the fermenter is reduced, resulting in a higher rate of productivity. The obtained seed culture is then utilised to inoculate fermentation medium. The inoculums are typically 1–10 percent of the total volume of the medium. Fermentation/bioprocessing processes are generally developed in stages, beginning in the laboratory and ending in the industry.

Scale–up refers to the process of developing an industrial fermentation process in stages. Scale–up is required to put a new fermentation technology created with mutant organisms into practise.  The goal of scale–up is to determine the best environmental and operating parameters for a successful fermentation industry at various scales, including substrate concentration, agitation and mixing, aeration, power consumption, and oxygen transfer rate. A fermentation technology is developed in 3–4 phases in a traditional scale–up.

A screening process using Petri dishes or Erlenmeyer flasks precedes a pilot project to find the best operating conditions for a fermentation process with a capacity of 5–200 litres. The final stage entails transferring laboratory-developed technologies to industry. It is important to remember that a fermentation process that works well in the lab may perform poorly or not at all at the industrial scale.

As a result, applying the laboratory settings of a fermentation technology created to industry is not always possible. On a laboratory scale, the highest yield of the product per unit time is of interest. Aside from product output, minimal operating cost is a significant factor to consider at the industry level.


The fundamental components needed to carry out fermentation are chosen according to the required volume based on the unique industrial fermentation process.

Contamination should not be present in the medium components. As a result, all of the medium components used in the fermentation are sterilised. Heat and, to a lesser extent, other physical means, chemical procedures (disinfectants), and radiation (using UV rays, rays) are used to sterilise.

Batch sterilisation takes 20 to 60 minutes at 121°C, while continuous sterilisation takes 24 hours at 140°C (30 to 120 secs). Batch sterilisation wastes a lot of energy when compared to continuous sterilisation, which saves 80 to 90 percent of the energy. Membrane filters sterilise air and heat-sensitive components.

Fermentation Process

It entails the microorganism’s multiplication as well as the generation of the intended product. The following is a breakdown of the fermentation process based on the cultures and mediums feeding strategies.

Batch Fermentation: The vessel is first filled with medium and culture, and then it is closed. Apart from oxygen, no other components are introduced after that. The pH of the solution is changed during the procedure by adding acid or alkali. The fermentation is allowed to continue for a set amount of time before the product is collected. Antifoam agents, such as palm oil or soybean oil, are used to prevent foaming. The heat generated is controlled by a water circulation system that circulates water around the vessel for heat exchange.

Continuous fermentation: This is a free-to-use system. It entails continuously removing culture medium and replacing it with new sterile medium in a bioreactor. This approach employs homogeneously mixed reactors, such as chemostat and turbid stat bioreactors. Antibiotics, chemical solvents, beer, ethanol, and SCP are just a few examples.

Fed batch system: It is a hybrid system that combines batch and continuous systems. As the fermentation progresses, extra nutrients are fed to the fermentors. Although the operation duration is extended, the products are collected at the end of the production cycle, just like in a batch fermenter.

Downstream Processing

Downstream processing refers to the operations that are utilised to recover usable products from industrial fermentation process. The cost of downstream processing (DSP) is frequently greater than 50% of the manufacturing cost, and product loss occurs at each step of the process. As a result, the DSP should be effective, efficient, and entail as few stages as possible.

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