Biomedical Engineering Reference
In-Depth Information
Disposable bioreactors have varied designs and purposes but all of them
are made of Class VI plastic films, are sterilized by gamma radiation, and
are disposed of after use; they may come with several attachments that
allow the filtration of media and monitoring of pH, DO, OD, pCO
2
, tem-
perature, and other PAT-related parameters. Use of stirrers and paddles,
and shaking and rocking the bags by mechanical or hydraulic means
achieve mixing and aeration inside the bag. A choice of aeration systems
may include surface aeration (e.g., in Wave Bioreactors) to forced sparg-
ing through proprietary ceramic tubes (e.g., MayaBioReactors). The host
cell yields obtained using disposable bioreactors match or exceed those
obtained in traditional reactors.
Disposable bioreactors come in many sizes, from milliliters to thousands
of liters; they can be equipped with bioinformatics systems that range from
very simple to very complex; they can be manual or highly automated; they
can be as inexpensive as a plastic bag to as expensive as the high-end tra-
ditional hard-walled bioreactors. The disposable bioreactor industry is still
evolving, with new inventions surfacing almost routinely. Here is a brief
look at their historical development over the past 60 years:
First Period—First Ten Years (1960s):
Petri dishes, T-flasks, roller bot-
tles, shaken plastic bags. At first, the glass petri dishes were replaced
by plastic plates, and the most significant development was the
use of polypropylene and Teflon bags by the Krolinska Institute in
Sweden to grow bacteria and yeast cells, albeit on a very small scale.
Second Period—Next Thirty Years (1970s to 1990s):
Disposable hol-
low fiber system, two-compartment system, multitry cell culture,
static bags for cell expansion, pneumatic mixing (peristaltic recir-
culation), and rocking bags. The hollow fiber technology required
recirculation of media to grow anchored or suspended animal cells
using the Cellmax HFBS (FiberCell), the AcuSyst-HFBSs (BioVest),
and the Xcell HFBS (BioVest). These bioreactors were able to operate
continuously for months at a time and helped produce quantities
ranging from a subgram to a few grams. Even though high cell den-
sities could be achieved, the problems of scaling up these bioreactors
ruled them out as a viable option for commercial production, and
they are used today to make small quantities of test substances.
The Cell Factory made of polystyrene was a flask-like culture system
containing a number of trays stacked in parallel in a single unit.
This was a good scale-up model for commercial production and
replaced roller bottles used for adherent cells.
CellCube from Corning Costar is similar to the Cell Factory, runs in
perfusion mode, and proves useful for adherent cell lines; it was
used for vaccine production on a limited scale and never showed
potential for commercial therapeutic protein manufacturing.
