Bioreactor Design and Operation - Bioprocess Engineering: Kinetics, Biosystems, Sustainability and Reactor Design - page 929

main limitation is that only volatile components can be monitored. On-line HPLC is
powerful for measuring levels of dissolved solutes, particularly proteins from geneti-
cally engineered cells. These devices require using liquid slipstream and sample prepa-
ration, usually micro or ultra filtration. HPLC instruments also require significant time
delays associated with sampling. Nuclear magnetic resonance (NMR) can provide
important information on intracellular metabolism for off-line or small-scale growth
experiments. In summary, current

instrumentation to monitor fermentors online is

very limited.
Having the physical characteristics of the bioreactor presents the next challenge d what to
do with it. Current fermentor design and control techniques are limited. Computer-
controlled fermentors are common, particularly at pilot plant scale. Typical computerized
control applications are for data logging, i.e. data historian. Computerized control systems
also provide regulatory control to open/close valves or turn on/off motors. Control loops
for DO, temperature, pH, and pressure control are also common. Automation of recipe
driven activities such as Clean-in-Place (CIP) or Steam-in-Place (SIP) is common, although
control based on cellular activity is limited.
One application involves control based on CO 2 in the off-gas, coupled with substrate
concentration in the feed and nutrient flow rates, allowing the glucose feed rate to be manip-
ulated to maintain glucose concentrations at an optimal level. This control strategy depends
on mass balances and gateway sensor concept. If glucose sensing is available, glucose control
can be accomplished with a feedback control system.
Good process control for fermentation awaits improved models of cultures, more sophis-
ticated sensors, and advances in nonlinear control theory.

18.7. STERILIZATION OF PROCESS FLUIDS

Sterility is an absolute concept. A system is never partially or almost sterile. On a prac-
tical basis, sterility means the absence of any detectable viable organism. In a pure
culture, only the desired organism is detectably present. The cost of contamination for
a bioreactor can be high. For example, undesired organisms can cause the waste of
substrate or generation of waste products, while bacteriophage can cause the decay of
fermentative organisms. The biocontaminant canbebacteria,fungi,yeast,viruses,etc.
In majority of the bioprocesses, elimination of biocontaminants is essential for the
success of the operation. In animal cell cultures, one often demands pure culture. The
presence of undesired organisms is often the basis for rejection of the batch. Disinfection
differs from sterilization in that a disinfectant reduces the number of viable organism to
a low, but nonzero number. Fluid streams can be sterilized in two ways: 1) physical
removal of cells and viruses (filtration) and 2) inactivation of living particles by heat,
radiation, or chemicals.
Sterilization of process fluids can be implemented batchwise or continuously. Batch ster-
ilization is suitable for batch operations and for sterilization of process equipment. For
continuous operations, continuous sterilization of process fluids (liquid medium, gas, and
suspensions) is more advantageous.