Biomedical Engineering Reference
In-Depth Information
cost-effective to operate it at a smaller than minimum level: the gap will be
filled by disposable bioreactors that can be readied almost instantly and
allow variable size production volumes. Flexibility in the future process-
ing industry would expedite the speed of drug delivery, allowing many
companies to make it to the market first and allowing the expansion of
biotechnology in such areas as cell therapy, stem cell applications, and
organ growth simulations.
Universal Use
Stainless steel bioreactors and fermenters have long served the industry
well as different cell lines and organisms were inducted as the workhorses.
There is no doubt about the versatility of this equipment. Disposable biore-
actors first appeared as flexible bags and in a 2D design that was ill-suited
to achieve the high K
L
a values to grow bacteria and yeast; they served well
for growing animal cells such as Chinese hamster ovary (CHO). The manu-
facturing industry did not embrace this well: why create separate systems
for bacterial culture growth and mammalian cell cultures if there were a
reactor available to growth bacteria? This could be easily modified to grow
animal cells. Compounded by the limited size of the disposable bioreactors
available initially, the idea of adopting them in the mainstream was lost. To
address this shortcoming, the major equipment manufacturers began devel-
oping 3D bioreactors wherein they could install similar mixing and aera-
tion systems as used in the stainless steel systems. Today, two companies,
Xcellerex and Thermo Scientific Hyclone, offer 2,000 L bioreactors for bacte-
rial fermentation. These are 3D stainless steel shells lined with disposable
liners embedded with mixers and aerators, just like the traditional stainless
steel bioreactors. The cost of ownership is perhaps higher than the stainless
steel system. While these options do offer many of the advantages of dispos-
able systems, the cost advantage can only be had if the industry starts using
2D bioreactors instead, which are much cheaper to construct, require no shell
structure, and can be operated horizontally. To overcome these technological
barriers, MayaBio developed stationary 2D bioreactors (
www.mayabio.com
):
by removing the movement of the bag (as it is required by GE's Wave), the
problems of integrity and size were eliminated. A horizontally lying 2D bag
can be used as long as needed; it is heated from underneath the table, and
the liquid inside the bag is moved by a patented flapper system that pushes
down on the bag to create a wave inside the bag. A slight inclination of the
bag provides both kinetic and potential energy to the medium, and K
L
a val-
ues into 100+ are readily obtained by aerating the media inside the bag using
a proprietary ceramic tube sparger. These 2D disposable bags can be used to
grow every cell and organism, and at a confluence and optical density (OD)
