Every wine aficionado knows that wine has to be swirled in a
glass in order for it to release its aroma. Applied to biotechnologies over
some fifteen years, this ordinary gesture has made it possible to develop more
efficient machines for culturing proteins in animal cells. The phenomenon has been
studied in detail at EPFL.
First, slowly pour. Then sniff. Then, keeping the base of
the glass anchored, apply a very light circular movement. Inhale again. Start
over, each time swirling the glass a little more strongly to aerate the wine.
This is how one goes about appreciating the complex bouquet of a fine vintage.
Nobody’s
contesting the legitimacy of this protocol; it’s something that everyone just
does more or less intuitively when presented with a grand cru or a cup of
coffee without a spoon. But as for precisely explaining the fluid mechanics
involved in this operation, known as “orbital agitation,”—well, that’s another
story.
Orbiting bioreactors
Professor Florian Wurm,
head of EPFL’s Laboratory of Cellular Biotechnology, has been developing
bioreactors that work on this principle for many years, based on the intuitive
understanding that orbital agitation results in a mixing action that is both
gentle and effective. The spin-off company that he has created to use reactors
of this type, ExcellGene, has just celebrated its tenth anniversary. “We now
are using small as well as large volume machines, to manufacture high value
recombinant proteins in animal cells,” he announces. “Most recently, in
collaboration with Kühner AG, the EPFL and the ExcellGene, one of the world’s
largest bioreactors based on orbital shaking has been constructed, with a total
volume of more than 3000 L.”
In traditional
bioreactors, the contents are mixed by a rotating platform that sits underneath
a container. By replacing these with orbital shakers (in which the entire tank
is moved), Wurm says he is able to significantly reduce the cost of
manufacturing proteins, which are used widely in the pharmaceutical industry. “The cultured cells receive fewer shocks, the mixture is more homogeneous, it
can be done in a normal air rather that in pure oxygen, and this technique
allows us to construct wider and shorter bioreactors, that are thus easier to
install in rooms of standard dimension, he adds. Moreover, we now use
disposable plastic bags inside the reactor, which cut most of the maintenance
costs.”
Complex waves
To go beyond empirical
knowledge and better understand what is really happening in an agitated
container, Martino Reclari, a PhD student in EPFL’s Hydraulic Machines
Laboratory (LMH), studied the movement that wine enthusiasts apply to their
glasses. “The form of the free surface, that which is in contact with the air,
is much more complex than we expected,” he explains. “As a result, the aeration
of the wine, that is, the exchange phenomena between the liquid and the
atmosphere, are very difficult to model.” Many different waveforms have been
described. “There is an infinite number of them,” he adds.
His work,
presented at a meeting of the American Physical Society, has made it possible
to understand the effect of two variables—the rotational speed and the
amplitude of the movement, both as a function of the dimension of the container
and the height of the liquid in it—on the waveform that will be generated. By
using video imaging, the scientists were able to determine that the liquid was
mixing not only from top to bottom along the wave that was forming on the edges
of the glass, but also from the center out to the edges. Reclari, who has been
in contact with the oenology section of the Engineering School
in Changins, has designed models to determine what kind of swirling motion is
most appropriate for a particular kind of glass and a particular kind of wine.
This small-scale
research can be extrapolated to meet the needs of those in the biotech
industry. “We have already determined that with three constant parameters, we
can reproduce the same waveform, no matter what size the container is,”
explains LMH Senior Scientist Mohamed Farhat. “Our numerical models, developed
with the Chair of modelling and scientific computing (Professor Alfio
Quarteroni) will enable us to calculate the optimal parameters to apply in
every specific case, including that of cell cultures.”