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Bioprocess Feed Automation Enabled through Software Scripts
Fed-batch fermentation, the most common mode of
operation in the bioprocess industry, is a modified
version of batch fermentation. Cells or microorganisms
are inoculated and grown under batch regime for a
designated amount of time, then nutrients are added
to the bioreactor in increments throughout the
remaining duration of the fermentation process. The
entire culture suspension is removed at the end of
each run. The start of feeding is normally determined
by substrate limitation in the broth, and the time
profile of feeding should be designed in a way that
the substrate remains non-excessive while cell
growth is fully supported. Because of the addition of
fresh nutrients, extensive biomass accumulation
normally occurs in the exponential growth phase.
Therefore, fed-batch fermentation is well suited for
bioprocesses aiming for high biomass density or high
product yield when the desired product is positively
correlated with cell growth. Also, because the cultures
are not overfed during the process, by-product accumulation
is limited.1
Why automated culture feeding?
As previously stated, the start of feeding is normally
determined by substrate limitation in the broth. How
does that look in practice? Feeding can be done
manually. The investigator typically takes a sample
from the bioreactor and measures the substrate
concentration. When it becomes too low, a feed solution
is added manually or by using a feed pump.
Sampling is done in intervals, like every hour or every
several hours. While this procedure is feasible, it has
some negative features. In addition to being a laborious
strategy, the investigator may miss the exact
time point of substrate depletion and at the point of
feeding the culture may be in a nutrient depleted
state already. In an automated feeding process in
contrast, feeding is started independently of a
sampling time point. Therefore, it can:
8 | GENengnews.com
* Prevent nutrient depletion
* Generate a more stable macro-environment
* Reach higher product yields
* Reduce manual workload
Improve standardization
How to automate feeding?
To automate feeding, two steps need to be taken:
First, it is necessary to install a device that drives the
feed solution in the bioreactor automatically. Typically,
this calls for use of a feed pump, driven by the
bioprocess control software. Second, the bioprocess
control software must be programmed to activate
and control the pump. This can be done using a software
script. The prerequisite: A bioprocess control
software with scripting functionality.
Software scripts are valuable tools to implement
tailored bioprocess control routines. They allow
process automation, by directing an actuator under
user-defined conditions and taking into consideration
relevant system or process parameters. Scripts offer
numerous possibilities; here we present two strategies
designed to optimize the culture feeding process.
Strategy 1: Time-based feeding
In a time-based feeding strategy, a defined volume of
feed solution is added to the culture per time increment.
One example is an exponential feed profile.
Here the feed rate is described by an exponential
function (Figure 1A). To vary the feed profiles, the
exponential factor of the equation is modified, with
higher factors leading to a faster increase of the
added feed volume per time unit.
To implement time-based feeding, the script text
is entered into the bioprocess control software, for
example DASware® control. The script contains the
formula defining the exponential feed profile, as well
as information about starting and ending the
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