Biomedical Engineering Reference
In-Depth Information
49.
Lab Chip
. 2006 Sep; 6(9):1229-35.
Epub 2006 Jul 27.
Microbioreactor arrays with
integrated mixers and fluid
injectors for high-throughput
experimentation with pH and
dissolved oxygen control. Lee
HL, Boccazzi P, Ram RJ, Sinskey
AJ. Research Laboratory of
Electronics, Massachusetts
Institute of Technology, 77
Massachusetts Ave, Cambridge,
MA 02139.
We have developed an integrated array of
microbioreactors, with 100 microL working volume,
comprising a peristaltic oxygenating mixer and
microfluidic injectors. These integrated devices were
fabricated in a single chip and can provide a high
oxygen transfer rate (k(L)a approximately 0.1 s(-1))
without introducing bubbles, and closed-loop control
over dissolved oxygen and pH (±0.1). The system
was capable of supporting eight simultaneous
Escherichia coli
fermentations to cell densities greater
than 13 g-dcw L(-1) (1 cm OD(650 nm) > 40). This cell
density was comparable to that achieved in a 4 L
reference fermentation, conducted with the same
strain, in a bench-scale stirred-tank bioreactor and is
more than four times higher than cell densities
previously achieved in microbioreactors. Bubble-free
oxygenation permitted near-real-time optical density
measurements that could be used to observe subtle
changes in the growth rate and infer changes in the
state of microbial genetic networks. Our system
provides a platform for the study of the interaction of
microbial populations with different environmental
conditions, which has applications in basic science
and industrial bioprocess development. We leverage
the advantages of microfluidic integration to deliver
a disposable, parallel bioreactor in a single chip,
rather than robotically multiplexing independent
bioreactors, which opens a new avenue for scaling
small-scale bioreactor arrays with the capabilities of
bench-scale stirred-tank reactors.
