Flow controllers for bioreactors and fermentation

What is Biotechnology?

Biotechnology is a technology that has been around for thousands of years but came into bright spotlight during the last 20 years. Why is that?

Biotechnological processes are conducted in a bioreactor, where substances are being synthesized with the help of bacterial, yeast- and cell strains. The end product is used in many areas of our daily lives, like yoghurt and beer brewing processes. Besides in food and beverage applications, it is also used in the field of medical drug research and production. Flow controllers play an important role in these Bioreactors. The rise of biotechnology and its growing field of applications are enough reason to find out more about this fascinating technology.

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The bioreactor, core of the process

Simply said, a bioreactor is a vessel in which biological processes take place. The bioreactors are equipped with either a simple manual control or more complex, fully automated, PLC control. Typically, the bioreactor process is a batch process and the time between start and harvesting is called a campaign.

The majority of bioreactors need to be supplied with gases and nutrients for growing bacteria, yeast or cells for the desired biological synthesis to take place. These additives are usually added continuously over a period of a few days to several weeks. Flow controllers play a significantly important role in the process control of Bioreactors. The differences in volume flow for either bacteria or cell cultures are significant.

Bioreactor, bioprocessing, fermenter market

Schematic overview of bioreactor process

The campaign of a process containing cell cultures can take up to three or four weeks before harvesting, while a campaign with bacterial cultures is often just lasting for a few days.

It is a challenge to carry out the process in a stable manner during this period of time and therefore, it is very important to accurately dose gases and nutrients. The differences in volume flow for either bacteria or cell cultures are significantly. The additive dosing is done in sterile conditions to prevent any contamination with unwanted bacteria that could compete with the microbial or cell culture.

In short, reliability and reproducibility are key in bioreactor processes, especially for flow control.

Aeration of bioreactors using flow controllers

The gases that are commonly used for the aeration of bioreactors are: Air, O2 (Oxygen), N2 (Nitrogen) and CO2 (Carbon dioxide). N2 is used to calibrate the Oxygen sensor (pO2) and to reduce the O2-content in the bioreactor at the beginning of the process. The bigger the number of bacteria or cells, the bigger is the O2 requirement. CO2 is used to regulate the acidity (pH) in the liquid phase. A bioreactor is usually controlled by checking the partial oxygen pressure pO2 and the pH in the suspension.

The cells’ intake of oxygen and all other substances are taking effect in the liquid phase. The oxygen must therefore be present in the liquid. To ensure this, it is attempted to add the oxygen – possibly as a component of air – in the smallest bubbles possible. Stirring the liquid will help distribute and diffuse the added oxygen.

The figure shows the ideal growth curve of a bacterial culture in a bioreactor

The history of bioreactors

The research and first production of microbiologically generated substances in medicines started during the second world war, when they discovered the advantages of using penicillin to treat the wounded soldiers. At that time, they discovered that using bacteria in microbiological processes have an advantage compared to the more conventional chemical synthesis. In chemical syntheses, many by-products are generated, some of them even in much larger proportions than the desired substance itself.

Bioreactor in use, bioprocessing, fermenter market

In biological syntheses however, one sees much higher yields of the target substance. In addition, this synthesis often offers simpler separation methods. Besides, bacteria, as well as human or animal cells, synthesize specific substances that are difficult or even inaccessible with conventional chemical synthesis.

In the last 20 years, powerful processes for isolating bacterial strains and other gene technological methods have allowed us to produce, isolate and multiply strains that do what they were developed for: synthesize target substances specifically, selectively and efficiently. In most cases, these syntheses are carried out in the so-called bioreactors.

Bioreactor applications

Bioreactors come in many different sizes and shapes suitable for a wide variety of applications. From the smallest reactors with a capacity of a few milliliters to large bioreactors of up to 100 m³. As a rule of thumb, one can assume that the oxygen flow is 0.1 to 0.15 times the working volume per minute for cell cultures and up to 2 times for bacterial cultures.

Food & beverage industry

Bioreactors are used in the production of foods and beverages for fermentation purposes, whether it is for addition of vitamins, colourants, flavourings, alcohol or antioxidants.

Take yoghurt for example. This is a product produced from the fermentation of milk in bioreactors. Yoghurt cultures are lactic acid bacteria. Or beer… for beer brewing processes yeast cells are used for converting sugars into alcohol. And what about cheese; originally, cheese is produced from milk by adding natural existing rennet, which is an enzyme from a plant or an animal. Nowadays, rennet for making cheese is produced by yeast cells that are grown in a bioreactor. All examples of bioreactor applications.

Micro-organisms have already been used for a long time in food production, but what are the reasons for the enormous increase in popularity of biotechnology since the second half of the 20th century?

Drug development and production

Biotechnology is becoming more and more important in drug development and production, as well as the multiplication of stem cells. Both are used for medical treatment. Time to market, cost reduction and consistent product quality are very important in designing and producing pharmaceutically active ingredients. Therefore, reliability of bioreactors and the possibility to scale-up the process from small to large sized bioreactors is very much desired.

Biobased chemicals and plastics

Other examples of biotechnological applications are biobased chemicals and plastics. Researchers are working on renewable plastics, which are made from organic materials with the help of enzymes and micro-organisms. There are already appealing examples of bio-based plastics such as toys, car parts and alternatives for PET bottles.

A specific example of bio-chemical production is using microalgae and sunlight for converting CO2. You can read our Application Note of a Belgium University about ‘Controlled CO2 supply for algae growth’

Application story about algae growth

Sustainable Energy

The transition to sustainable energy is another driver that boosts the use of bioreactors. Biogas and biofuel in the form of biomethane, bioethanol and biodiesel are gaining popularity in our home, industrial and transport energy supply. The gas or fuel is created as a result of fermentation of organic material such as dung, sludge, organic waste, grass, corn, sugarcane. The fermentation tank, which is kept at a temperature of 38-40 ° C and is being stirred, is in fact a bioreactor.

Biotechnology and bioreactors: a very diverse technology