The overview of suitable bioreactors for plant cell and tissue cultures indicates that the basic technology for production of plant-derived products in bioreactors is essentially in place. But the production of plant-derived products in bioreactors is often not economically viable compared with de novo synthesis. Exceptions are high-value products. Yoshioka and Fujita (97) and Goldstein (98) demonstrated that capital investment is an important instrument for reduction of secondary metabolite production costs. A possible key issue here is the bioreactor, with its high substantial costs based on requirements for aseptic bioprocess technology, sterilization in place (SIP), cleaning in place (CIP), and validation possibility including sophisticated instrumentation. In addition, costs for upstream processing and downstream processing as well as personal training have to be considered. The current price of a 100-L standard sterile reactor is estimated as $100,000 to $140,000. This price includes 30% costs for the bioreactor, 30% costs for instrumentation, 15% costs for piping, 10% costs for engineering, and 15% costs for qualification as well as the validation procedure. Increasing reactor size will result
in a proportional increase of costs. The costs concerning instrumentation, engineering, qualification, and validation will stay approximately at a constant level. This is underlined by the fact that the investment costs for a 500-L reactor are between $175,000 and $200,000 and the costs for a 10-m3 reactor are between $400,000 and $450,000 (H. Schindler, MAVAG Ltd., Switzerland, personal communication, 2000).
A rethinking of the current reactor technology combined with a rational and simple reactor design using disposable materials is needed for a remarkable reduction of reactor costs influencing capital costs. This idea resulted in the development of a new bioreactor generation for plant cell and tissue cultures (disposable and low-cost bioreactors). At present, three types of such bioreactors for mass propagations of plant cell and tissue cultures have been proposed in the literature (26,99-101).
The so-called plastic-lined reactor with working volumes of 6.5 and 28.5 L based on an airlift reactor guarantees the mass propagation of Hyoscyamus muticus suspension cells. About 7 g dry weight of plant cells per liter of medium were grown in 13 days in the 28.5-L low-cost airlift reactor (99).
The wave reactor (Fig. 11) is a mechanically driven reactor system. This reactor system, available on the laboratory scale (working volume of 10 L) and pilot scale (working volume of 100 L), consists of three components: a rocker base unit, the disposable bioreactor chamber, and the measuring and control units. Here the energy input is caused by rocking the chamber forth and back, putting the cell culture and the medium in a wave movement. In this way, the surface of the medium is continuously renewed and bubble-free aeration can take place. Depending on the sensitivity of the cultivated cell line, the angle and amplitude of the rocking motion as well as the velocity can be varied. Specially designed sterile plastic cell bags that guarantee simple handling as well as optimal cell growth for hairy root cultures, suspensions, and embryogenic cultures have the function of the bioreactor chamber.
The wave laboratory reactor has shown a higher biomass increase for tropan alkaloids as well as for ginsenosides producing hairy root cultures (about 40% higher) and embryogenic cultures of Allium sativum (about 20% higher) compared with optimized stirred reactors, rotating drum reactors, and droplet phase reactors used in experiments for growth comparison (100).
Another low-cost system is the immersion reactor RITA of the French company CIRAD. The system has proved its efficiency for cultivation of embryogenic cultures of banana, coffee, citrus, oil palm, and rubber (101).
These low-cost reactors can thus enhance biomass productivity tremendously and may also have an economic advantage. It seems likely that
such low-cost reactors represent interesting alternatives to other suitable standard bioreactors on the laboratory and pilot scale.
New low-cost as well as disposable reactor systems will be available on the market in the near future, such as a low-cost mist bioreactor for the production of bioactive compounds in transformed hairy root cultures (E. Wildi, ROOTec Ltd., Germany, personal communication, 2001).
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