EPPENDORF_Nov2021_UpstreamBioprocessingImprovingEfficiency - 10

Bioprocess Feed Automation Enabled through Software Scripts
An inline or online analyzer transfers its reading to
the bioprocess control software. Inline sensors are
placed inside or at the vessel and measure process
values in real-time, without the need for sampling.
Online sensors deliver process data almost in realtime,
after automatic sampling.
Based on this value, the software script activates
an actuator. Activity of the actuator controls the
process parameter of interest at setpoint. After
considering these general guidelines we now
consider specific sensor-based feeding strategies:
1) Feeding based on a DO spike
Principle: The DO concentration of the culture
medium is influenced by the amount of air supplied
to the bioreactor and the oxygen consumption of the
growing cells. In the course of the bioprocess run it
will decrease, reflecting the oxygen consumption of
the growing cells. If the carbon sources are depleted,
the cells' metabolic activity and therefore their
oxygen consumption suddenly decreases, leading to
a spike in the DO concentration (Figure 3A). The DO
spike therefore indicates substrate depletion and can
be used to trigger automated culture feeding.
Implementation: To automate feeding based on
the DO spike, a script can be implemented in the
bioprocess control software (e.g. DASware control).
The DO spike is defined as the DO sensor readings
from a lower trigger point to an upper trigger point.
Upon reaching the upper trigger point, the feed
pump is automatically activated. Usually preliminary
studies are required to gain information on the DO
spike of the culture of interest.
DO sensor: Inline DO sensors are routinely used in
almost any bioprocess.
Feeding based on a DO spike is particularly suited
for microbial cultures with a high oxygen demand.
10 | GENengnews.com
Figure 3: Schematic representation of the possible course
of DO (A) and substrate concentration (B) in a bioprocess.
2) Feeding based on substrate concentration
Principle: The concentration of a relevant substrate
(e.g. glucose) is directly measured. If it drops below a
threshold, feeding is initiated (Figure 3B).
Implementation: Inline analytics of substrates often
involves the integration of third-party analyzers with
the bioprocess control system. The seamless integration
with the bioprocess software, which is receiving
the analyzer's signals and at the same time controlling
actuators of the bioprocess system, including pumps
or gassing devices, is the key to their convenient use.
Open Platform Communication (OPC) facilitates the
communication of devices of different origins.
Substrate sensors: Raman analyzers and TRACE
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