Fermentation - Food and Industrial Bioproducts and Bioprocessing - page 197

Another recent trend in fermentation is the use of disposable bioreactors instead of
stainless steel reactors for process development, especially in pharmaceutical manufacturing
(Hanson et al ., 2009). Disposable bioreactors are typically plastic devices, such as microtiter
plates, T-flasks, shake flasks and wave reactors, with different sizes. Disposable bioreactors
can be used as a seed fermentor or as a production fermentor for products on a small scale
(Mikola et al ., 2007). The main advantages of disposable reactors include more flexibility
in operation and use for different products, elimination of cross-contamination, less time
needed to set up because the reactor is ready to use, low cost and less labor needed. However,
disposable reactor sizes do not exceed 2,000 L because of physical limitations, stability
issues and heat and mass transfer limitations, as these reactors do not have impellers for
mixing. In addition, disposable plastic reactors may leach chemical components into the
media that could negatively impact the quality of the final product (Hanson et al ., 2009 ).
Another emerging application in fermentation is the use of high throughput miniature
(mL scale) bioreactors (HT MBR) for assessment of microbial systems for strain screening,
nutrient optimization and productivity screening (Isett et al ., 2007 ). The advantages of HT
MBR compared to conventional shake flasks are lower labor and material costs and higher
throughput because of the ability to run many cell cultivations in parallel. However, HT
MBRs do not contain online sensors and do not provide enough samples for offline analysis
due to their small size. Several miniature bioreactors, such as microwell plates (

L scale),
miniature stirred bioreactors and miniature bubble column bioreactors, have been reviewed
by Betts and Baganz (2006).
The use of disposable bioreactors and miniature bioreactors resulted in new developments
in online sensor technology to enable direct measurements of pH, dissolved oxygen, optical
sensing for cell concentration, fluorometry and infrared spectroscopy (Glindkamp et al .,
2009). Fluorescence sensors are used to measure several analytes, such as proteins, vitamins,
glucose, ethanol, ATP, NAD(P)H and pyruvate, by scanning the excitation and emission
wavelengths for these compounds. Infrared spectroscopy (IR) can be used to measure
glucose, fructose and ethanol concentration in the fermentation medium. IR can also be used
to monitor gas phase composition, in particular carbon dioxide. Online sensors will help to
improve control of fermentation processes. These sensors should be low cost and reliable,
which may be challenging if the sensors are disposable.

μ

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