Automation Applications in Bio-Pharmaceuticals

Chapter 3.10.1 - Typical Instrumentation Requirements

Bioreactor instruments range from the simple to the most complex. In
many cases, the more complex instruments may be off-line bench-type
instruments. Instruments may be mounted directly on the vessel, or they
may be on a side-stream coming from the vessel: either a recirculation line
or a harvest line.

Temperature

Bioreactor temperature measurements are most commonly placed in
thermo wells. RTDs and thermocouples are most often used. In large vessels,
there may be sensors at many levels throughout the vessel, to ensure
uniformity. When deciding the placement of temperature measurements,
be sure to consider both operational and SIP requirements.

Pressure

Pressure measurement is typically handled by a pressure sensor located
upstream of a vent filter. This keeps the instrument away from the contents
of the vessel.

Air Flow

In aerobic reactions, maintaining air flow is critical to the rate of reaction.
Good air flow measurement is important. This is typically done with a
mass flow meter. To prevent contamination, it is a good idea to keep a filter
between the inlet airflow meter and the bioreactor.

Dissolved Oxygen and Other Gas Analyzers


Measuring dissolved gases in bioreactors can be critical. In many cases,
these variables are brought into a closed-loop control strategy. Dissolved
gas composition is measured with membrane-type sensors. Extra care
must be taken in selecting a probe that can withstand CIP and/or SIP
cycles. The sensor may be mounted through the wall, in a circulation line,
or as an off-line measurement.

pH

pH measurement also requires a probe in contact with the process fluid.
Again, care must be taken in the selection of a probe that can withstand
the chemical and temperature extremes of CIP and/or SIP cycles. In some
cases, the pH probe may be removed and cleaned out-of-place.

Composition Measurement

Analytical composition measurements have traditionally been performed
off-line, but newer technologies are bringing more and more on-line capabilities.
Again, locate the instrument close to the sample point to avoid
erroneous readings.

These instruments often use very small capillary sample tubes. You will
need to take care to provide a way to flush out these lines or replace these
tubes frequently to prevent plugging or contamination.

Level Measurement

Level measurement in a bioreactor can be complicated by foaming,
splashing, and changes in liquid density. In earlier days, these were handled
by using a simple sight glass. However, sight glasses proved hard to
clean and sterilize, and are not easily applied in today's environment. This
leaves us with capacitance probes, pressure probes, and ultrasonic and
radar methods.

The type of level probe depends upon the specific application. Be sure to
work closely with process engineers to understand what is happening
inside your bioreactor. Table 3-2 illustrates some of the strengths of each
type of level measurement.

Table 3-2 Strengths of Various Level Probes (Foam, Density Changes, Cleanability)

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