Bioreactor - Overview and Benefits

Many different types of laboratory fermentors and bioreactors are used worldwide, but the selection of a good quality bioreactor is not easy. Some advantageous parameters found in one product are cancelled out by other drawbacks in the same system. We have put all the innovations together and released the new LAMBDA MINIFOR Bioreactor, which satisfies most requirements of modern biotech laboratories.

REDOX potential measurement system

LAMBDA REDOX allows the measurement of the Red-Ox potential and the digital transfer of the data to the PC through its RS-485 interface. The measured data can be visualized and recorded for example by the fermentation software SIAM.

The measurement of Red-Ox potential can be made with the laboratory fermenter-bioreactor LAMBDA MINIFOR, using a sterilizable combined pH/temperature probe with an additional Pt electrode fixed on its glass body. This probe is connected to the MINIFOR fermenter-bioreactor in the same way as the standard pH probe.

It does not require any additional connector, cable or side neck. However, the MINIFOR fermenter-bioreactor must have been equipped with the redox option in advance. The output RedOx signal is then provided on the “PUMP” socket at the rear side of the MINIFOR laboratory fermentor-bioreactor base unit.

Medium cooling without cooling water

LAMBDA Peltier electronic cooling loop for MINIFOR fermenter-bioreactor

Cooling with this device is based on the electronic cooling effect produced by the flow of electric current through a Peltier cell. The Peltier cell allows cooling of the medium without the necessity of other means such as a refrigerating compressor or cooling water baths. LAMBDA has selected a cooling loop working according to the "heat pipe" principle, which has an advantage of having up to 80 times higher heat conduction compared to copper (!) and can be used with various levels of medium. It works even when the loop is not entirely submerged in the medium.

The LAMBDA Peltier cooling system is extremely compact and advantageous when cultures should be run at temperatures close to room temperature or a few degrees below room temperature. Lower temperatures can be achieved by isolation of the vessel with convenient isolating material. The LAMBDA Peltier cooling loop eliminates the need of refrigerated circulating baths, which are expensive and take a lot of valuable bench surface.

Combined with the infrared-heating system of the MINIFOR bioreactor unit it offers very precise temperature control of the cell culture.

Self-cleaning micro-sparger

• Common air spargers are frequently clogged especially in mineralized media. Due to the air flow the medium progressively dries out on the edge of the sparger orifices (openings) and eventually blocks them completely. This stops the air inflow and the run has to be aborted.
• LAMBDA introduces a self-cleaning micro-sparger, which due to its elasticity does release any deposits formed on the sparger holes and thus guarantees gas inflow at all times.

Maximal accessibility and visibility

• A cascade casing guarantees overall easy visibility, accessibility and handling.
• The display showing all parameters and control buttons is located in the front.
• Very good visibility into the vessel which is fixed on the first platform above the infrared radiator.
• Easily accessible probes, ports, tubing and stirring connections.
• Storage of bottles next to reactor quickly fixed and changed in position by magnetic holders.
• Good accessibility of the pumps which are positioned on freely adjustable support plates above reactor vessel and provide shortest possible tubing connections to the reactor vessel.

Autonomous precise gas flow control modules

• The LAMBDA MASSFLOW is a new mass flow controller system specially developed for the precise flow measurement and control of gases. It uses a high quality laminar mass flow sensor that has a very low pressure drop. The gas flow (e.g. air, oxygen, nitrogen, carbon dioxide, ...) is continuously measured and controlled.
• The flow rate is regulated by a special proprietary proportional needle valve controlled by a microprocessor. The flow rate can be programmed and the transferred gas volume totalized with the optional FLOW INTEGRATOR.
• With LAMBDA MASSFLOW the user can set up high quality gas control facilities containing one or more different gas streams according to his specific needs and is not forced to use common expensive four-gas-stations.

Two PC fermentation software packages at the cost of one

Apart from the direct control of the parameter on the display, a process control system (PCS) for fully automatic control of the batch and data storage is available:
FNet, an easy to use fermentation software for common cultures and up to 6 MINIFOR bioreactors is supplied in one package together with SIAM, a top notch industrial instrument control software which can make almost everything and is unlimited in the number of instruments being controlled. It is upon to user which one he prefers to use. No additional licenses for additional bioreactors are required!

Flow INTEGRATOR reveals valuable culture information

• The LAMBDA INTEGRATOR allows to record how much liquid or gas has been pumped as a function of time. This information was not available until now. Examples are:
  • information for the regulation of reaction conditions such as pH, temperature or other parameters
  • information about the kinetics of the respective process
  • completion or disturbances that have occurred during the process

• The LAMBDA INTEGRATOR allows a simple and precise integration of the amount of liquid delivered by the pumps or gas delivered by the MASSFLOW gas flow controller. The electric impulses moving the stepping motor are registered and transformed into a direct current. The resulting voltage can then be measured and recorded. This data yields important information about the culture growth, its kinetics and time of completion.
• The INTEGRATOR can also be used for measuring of enzyme activity (e.g. esterases, amidases, lactamases and other enzymes). It can be placed below the peristaltic pump and does not require additional bench space

Extremely compact bioreactor system

• Covers the whole laboratory-scale culture volume range from 35 ml to 6 liters
• Extremely compact than any bioreactor system on the market
• Smallest bioreactor foot print - comparable to the size of a sheet of paper (A4)
• Minimized instrument dimensions - number of times smaller than the existing traditional systems
• Weighs only 7.5 kg - no other bioreactor system could be lifted by a child
• Despite of its compact size, the bioreactor allows a perfect access from all sides!

Optimized bioreactor vessel design

The very expensive, clumsy and complex to set up traditional metal head plates were completely eliminated (see Elimination of expensive head plates) and replaced by new threaded glass vessels, which make ports manipulation as easy as screwing a cap on a bottle!

The LAMBDA fermentation vessel has one central neck with large threads for fast and reliable fixing of the agitating and aeration system. This can be easily done just with one hand.

• Eight additional threaded necks are distributed around the side of the vessel (7 small necks and 1 larger neck for quadruple sampling and addition ports) - all well accessible from all sides
• Multiple ports and other implemented solutions make the MINIFOR configuration equivalent to 16 classical ports.
• The side necks are made tight by special elastic stoppers, which have very long contact surface and multiple seals to prevent any contamination. These stoppers are permanent and may be used a great many times. Therefore, operating and maintenance costs are extremely low. The stoppers are easily kept in place by threaded caps.

Revolutionary radiation heating

• The vessel is heated from underneath by infrared radiation generated by a spiral heater of high heating power but very low heat capacity.
• Heat rays are concentrated by the gilded parabolic reflector with 98 % efficiency onto the bottom of the vessel, where about 50% is absorbed by the glass and about 50% is absorbed directly by medium. The result is an extremely soft heating without any hot spots, not even at lowest medium levels.
• Natural thermal convection takes place even without any mixing of the culture.
• Due to the low heat capacity of metals (corresponding to heat capacity of one ml of water!), the precise dosing of the supplied heat allows a very accurate control of the temperature in the medium
• This novel heating system is also very convenient, because cables, tubing, connectors, the necessity of heating blankets or jacketed vessels and circulating water supplies are completely eliminated
• This new system outperforms all other heating systems

Easy weight control for continuous cultures

• The amount of medium in the MINIFOR fermenter-bioreactor can be kept constant by using a special weighing module placed under the front edge of the instrument. The harvesting pump will automatically keep the weight of the culture constant.
• Continuous cultures (chemostat) allow a considerable increase in productivity. In an equilibrated dilution state, culture parameters can be studied more efficiently than in a batch.

Elimination of expensive head plates

• Typical fermentation vessels require a rather complex fixing of head plates with many and very closely spaced ports and screws.
• Heavy head plates are expensive and the accessibility of all ports on their top is bad, especially in the case of low volume vessels.
• A new head plate is necessary for each vessel of different volume which leads to high additional costs.
• Threads of ports in head plates are shallow. This, together with the well-known o-ring flattening after sterilization, leads to contaminations.

Highest pump quality for continuous cultures

The high quality LAMBDA peristaltic pumps PRECIFLOW, MULTIFLOW, HIFLOW, MAXIFLOW and MEGAFLOW have been specially developed for long term continuous processes like fermentations and cell cultures:

Feed pump and harvest pump (fed-batch culture, continuous culture, chemostat, turbidostat, perfusion)
Controlled addition of nutrients, minerals
pH control (addition of acid, base, buffers)
Antifoam control (addition of antifoam agent)
Sampling at particular time interval
Feed flow rate profile
Sample addition/injection
Follow growth kinetics
Quantify the metabolic activity of the culture
Media dispenser
Process optimization with C-feed in fed batch
Pump media with foot switch for filling agar plates

LAMBDA's unique tubing compressing mechanics reduces pulsation and is very gentle to the tubing. No clamps, fixings or stoppers are required to hold the tubing in place. This leads to a long tubing life and the long term stability of flow rates even with low cost tubing.

The tubing economy is such that the LAMBDA PRECIFLOW peristaltic pump is paid back after the use of only 80 m of tubing. Thus, this is the only pump on the market, which saves more money than it costs!

Fully independent control

• The LAMBDA MINIFOR bioreactor can be fully controlled and operated from the front panel. Together with the probes, controllers and pumps it forms an autonomous unit. All parameters can be immediately seen without any scrolling and can be adjusted from the front panel situated on a well visible place just in front of the culture vessel.
• Each MINIFOR has its own two microprocessors and complete regulation electronics. This ensures a continuous measurement, immediate response and the control of all parameters. Such a system is much superior to a partial, sequentially controlled system, where two or more vessels are put on one common control unit, sometimes also called tower. This makes each MINIFOR unit a completely independent bioreactor!

New low dead volume cell retention disc

Coming soon:

LAMBDA is testing a new modular cell retention system, where the total filter surface can be selected by the user. This cell retention system will have efficient automatic back washing and an extremely small dead volume. In comparison to so-called spin filters this innovation will considerably increase the efficient volume of the bioreactor and fouling will also be reduced.

Novel non rotational mixing

• We have rejected the commonly used stirring of medium by rotation (which is almost a dogma in the field). We were amazed to see how many advantages (at least in the laboratory scale) are obtained by a simple reciprocating up and down movement of stirring discs.
• It is possible to get an easy and complete separation of the inner and outer environment of the bioreactor just by using a simple inexpensive elastic membrane. The results are comparable (if not even better) to the much more expensive magnetic coupling.

Unique easy sterility construction

• Elimination of critical points makes the keeping of bioreactor sterility easy. A strong silicone membrane isolates completely the vessel from the outer environment. The sterility is thus equivalent to magnetic coupling, but is considerably less complex and much less expensive.
• All o-rings have been replaced by large silicone stoppers with multipoint seals. They are permanent and need not be replaced frequently as is the case with o-rings, which become flat after sterilization.

Precise electronic gas flow control

• A precise electronic mass flow controller automatically adjusts the pH and pO2 by proportional and continuous gas flow control
• The gas flow measurement and proportional needle valve are microprocessor-controlled
• Exact gas volume information

Exceptional volume range in one instrument

As there has been a lot of progress in analytics and sample preparation methods it is now possible to use, with advantages, much smaller volumes of media in smaller vessels than it was before. The MINIFOR fermenter-bioreactor has been conceived so that reliable results can be now obtained in much lower volume than before. No need to use 14, 10, 7, 5, 3 l vessels to study and optimize the living conditions of the cellculture. This can be successfully done in just one liter vessel. The MINIFOR fermentor/bioreactor allows you to work with volume ranging from 35 ml to 6 liters in one single instrument.

• small volumes of medium are faster sterilized, cooled down and are ready in less time
• less medium costs
• in MINIFOR a higher volume of sample can be withdrawn without any effect on the quality of regulation
• to increase productivity continuous cultures are possible. Minifor is ready to receive an optional scale module (channel X)
• lower downstream costs
• lower disposal costs

New softest agitation – the “Fish-Tail”

• A special "fish-tail" stirring disc based on the principle of the tail of a fish has been developed. The up and down movement of one or more "fish-tail" stirring discs provides gentle mixing both in horizontal and vertical direction. At the same time this type of stirring is more efficient and it eliminates cutting edges and micro-eddies formed by all common impellers used in bioreactors. As a consequence, the cell viability is increased.
• In analogy to a fish tail, this shape of the stirring disc produces a long range movement of the liquid (culture medium). No other stirrer type provides a similar positive combination of advantages for the agitation in cell cultures.

Automatic recognition of the culture volume

• A very compact control system, which will allow good measurement and control of all important parameters by the same unit, is preferable for the user. Living organisms are extremely complex and it is desirable to measure and control as many parameters as possible. This will help to identify problems when they possibly arise.
• Therefore, we decided to measure and control the five most important parameters: temperature, pH, pO2, air flow rate and stirring. In addition, we wanted to provide the option of controlling one supplementary parameter such as weight, glucose concentration, conductivity, redox potential, optical density (OD) and the like. For this reason, one selectable and controllable parameter "X" has been included. All readings can be seen at a glance without the necessity of scrolling or selecting menus.
• The quality of regulation especially in PID controllers depends on the right setting of constants. From experience we know, that only few users know how to set these parameters properly. LAMBDA therefore leaves this task to the microprocessor which monitors what is going on in the current process and sets the right constants continuously. The working volume is recognized from the heating response on medium temperature and the most appropriate parameter setting is made automatically.

World smallest antifoam control system

To spare the space around bioreactor vessels, LAMBDA has developed the smallest anti-foam control system consisting of a miniature foam detector ANTIFO and a subminiature syringe pump DOZITO.