Biomedical Engineering Reference
In-Depth Information
11.
Biotechnol Bioeng
. 2010 Oct 15;
107(3):497-505. Microfluidic
biolector-microfluidic bioprocess
control in microtiter plates.
Funke M, Buchenauer A,
Schnakenberg U, Mokwa W,
Diederichs S, Mertens A, Müller
C, Kensy F, Büchs J. AVT
Biochemical Engineering, RWTH
Aachen University,
Worringerweg 1, 52074 Aachen,
Germany.
In industrial-scale biotechnological processes, the
active control of the pH value combined with the
controlled feeding of substrate solutions (fed-batch)
is the standard strategy to cultivate both prokaryotic
and eukaryotic cells. On the contrary, for small-scale
cultivation, much simpler batch experiments with no
process control are performed. This lack of process
control often hinders researchers in scaling up and
scaling down fermentation experiments, because the
microbial metabolism, and thereby the growth and
production kinetics, drastically changes depending
on the cultivation strategy applied. While small-scale
batches are typically performed highly parallel and
in high-throughput, large-scale cultivations demand
sophisticated equipment for process control, which is
in most cases costly and difficult to handle.
Currently, there is no technical system on the market
that realizes simple process control in high
throughput. The novel concept of a
microfermentation system described in this work
combines a fiber-optic online monitoring device for
microtiter plates (MTPs)—the BioLector
technology—together with microfluidic control of
cultivation processes in volumes below 1 mL. In the
microfluidic chip, a micropump is integrated to
realize distinct substrate flow rates during fed-batch
cultivation in microscale. Hence, a cultivation system
with several distinct advantages could be
established: (1) high information output on a
microscale; (2) many experiments can be performed
in parallel and be automated using MTPs; (3) this
system is user-friendly and can easily be transferred
to a disposable single-use system. This article
elucidates this new concept and illustrates
applications in fermentations of
Escherichia coli
under
pH-controlled and fed-batch conditions in shaken
MTPs.
