Lab Scale Bioreactors and Fermenters FAQs

In simple terms, bioreactors are defined as vessels in which a biological reaction (bioprocess) takes place under a controlled and specific environment. Bioreactors are often used to cultivate a range of cell types (including mammalian cell lines and stem cells), microorganisms (such as fungi, yeasts and bacteria) and algae.

The Froilabo lab scale bioreactors have options for both microbial fermentations and cell culture cultivation processes. These bioreactors are commonly used in academia, research, process development & optimisation, scale up and production.  Possible bioreactor applications include the manufacture of yeasts, enzymes, bio-fertilizers, vaccines, probiotics, bioplastics, mammalian cells, cultured meat, etc.

Benchtop bioreactors have a small footprint, meaning they take up little space on a lab bench.

Froilabo offer three bioreactors with the following total volumes: 1-, 6- and 15- litres. Each is autoclavable.

Bioreactors can be categorized by physical characteristics and by the size of production. The physical characteristics include the vessel volume, the number of vessels per controller and the reusability of the vessel (autoclavable or single use). Production scale can be divided into 3 groups: lab-scale (0.5 – 10 L), pilot-scale (10 – 500 L) and industrial-scale (500 L upwards).

In the twin 1 L bioreactor, the temperature control system is equipped with a Peltier element. This enables temperature control without the need to connect to a cooling water source. This also applies to the cooling of the condenser.

The 6 L and 15 L bioreactors feature a metallic jacketed base, through which water will flow, which is thermoregulated by the built-in thermostat. This is a safe and reliable method, and an easy solution for temperature control.

Configurable peristaltic pumps with variable speed come as standard on all Froilabo lab-scale bioreactors. Each pump may be configured to one of following titration functions: base, acid, or foam-level. The 6 L and 15 L bioreactors have 3 pumps, and the 1 L bioreactor has 3 variable speed peristaltic pumps. Additionally, external peristaltic pump can be connected, controlled by a 4-20 mA signal.

In the basic version the following variables can be controlled:

• Temperature
• pH
• Dissolved oxygen
• Antifoam levels.

Optional controllable variables include:

• Overpressure
• Methanol/ethanol concentration.

Optional measurable variables include:

• Concentration of Oxygen, Carbon dioxide and other gasses in outlet gas flow
• Redox
• Conductivity
• Dissolved carbon dioxide
• Cell density (total cells, viable cells)
• Ethanol/methanol concentration
• Volumetric oxygen mass transfer coefficient k_La.

This can be added as an option in the 6 L and 15 L bioreactors. An autoclavable pressure sensor can be installed, as well as an electrically controlled valve that is connected after the outlet filter. Overpressure can be controlled up to 1.6 bar.

The volumetric oxygen mass transfer coefficient – kLa, is the parameter that controls the rate of oxygen transitions from the gas phase into the liquid phase. kLa shows numerically how efficiently oxygen, which is introduced through a sparger in the vessel, is dissipated and distributed in the medium by the mixer. In principle, kLa can be used to calculate the oxygen uptake rate, which correlates with biomass growth. This means that by monitoring kLa the growth of microorganisms can be evaluated in real time.
To calculate kLa automatically the bioreactor must be equipped with Oxygen and Carbon dioxide gas analysers.

There are two main options – The standard Rushton turbines or pitched blade impellers.

Standard Rushton turbine mixers are recommended for bacterial and yeast microorganisms, while pitched blade impellers are more suitable for shear-sensitive cell culture and viscous fermentation media. Both solutions are provided with magnetically coupled mixers.

Additionally, mixers can also be customized for specific applications.

All Froilabo lab scale bioreactors feature magnetically coupled mixers. The mixing intensity is ensured by applying high mixer rotation speeds and mixers with parameters corresponding to real Rushton standard turbines. The maximum mixing rotation speed in the 1 L laboratory bioreactor is 2000 rpm, in the 6 L is 1300 rpm, and in the 15 L is 750 rpm.

Yes, oxygen enrichment is available in all models. In the basic version it uses two solenoid valves. Optional Thermal Mass Flow Controllers (TMFC) can be used to control the air and oxygen supply.

In all our laboratory bioreactors three DO cascades are available: mixer rotation speed, oxygen enrichment and substrate feeding. The number of cascades is selected before the process. In the feeding cascade, the initial feeding rate of the substrate is set according to the adjusted profile (if a fermentation has been run according to the adjusted profile before) or with a defined maximum substrate feeding limit (if there has not been a feed before).

There are two options.

1. In the basic version it is done by adjusting time dependent feeding rate profiles. Between two defined feeding points a step wise, linear, or exponential profile can be selected.
2. We also offer model-based feeding control. Using this method feeding rates are controlled automatically by a program which optimizes the dosage based on mathematical models

Polarographic, optical and Hamilton ARC sensors can be used. ARC sensors send 4-20 mA signals directly to the PLC allowing simultaneous information management via Bluetooth in smartphones or PC installed programs. This program generates a report about all calibration procedures, sterilisation numbers, predicted service life. The lifetime of these sensors is longer compared to other types.

1. Different mixing conditions. For cell culture bioreactors, a sensitive shear mixer (in our case pitched blade impeller) is used with lower maximal revolutions speed.
2. Instead of a ring sparger, a micro sparger is used, and gas supply is also overhead instead of underneath.
3. Usually, the bottom sparger mixes four gasses (Air, oxygen, nitrogen, and carbon dioxide). Conversely, in the overhead only two gasses are mixed (Air and carbon dioxide)

Froilabo Bioreactor process control is based on Siemens Simatic S7-1500 controllers. It is characterized by its high reliability and includes international service in any country with a Siemens office.

The SCADA is our own user-friendly development. It is based on the ARC Informatique PC Vue industrial development package, which gives wide possibilities for process data management and reporting according to the requirements of 21 CFR Part 11 (document from US Food and Drugs administration).

Yes, with the remote-control function integrated in the SCADA bioreactor software the bioreactor fermentation process can be managed using a laptop, tablet, or smartphone from outside the laboratory.

Yes. Our bioreactors are connected to internet with the help of Tosibox. The Tosibox allows remote access to our customer’s bioreactors control systems through the Internet. It is used for remote maintenance and program updates. Customers in need of support can contact Froilabo who can connect remotely to the bioreactor control system to diagnose the problem and give advice on how to solve it.

Effective mixing of the culture within the bioreactor is important to ensure even distribution of nutrients and temperature etc. and to avoid pockets which deviate from the ideal environment. The mixing speed is also crucial and is dependent on the cell line and how tolerant it is of shear stress. Typical mixing rate: