BioVT-2010-13 [BibTeX]
Matthias Funke, Andreas Buchenauer, Uwe Schnakenberg, Wilfried Mokwa, Sylvia Diederichs, Alan Mertens, Carsten Müller, Frank Kensy, Jochen Büchs:
Microfluidic biolector-microfluidic bioprocess control in microtiter plates
Biotechnology and Bioengineering, 2010, 107(3), 497-505
Abstract:
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 cultivations,
much simpler batch experiments with no process control
are performed. This lack of process control often hinders
researchers to scale-up and scale-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.
Keywords:
microfluidic chip, micropump, microtiter plate, shaken bioreactor, BioLector, process control, pH-control, fed-batch
Wenn Sie Interesse an einer elektronischen Kopie haben, benutzen Sie bitte unser Onlineformular