lly to a BioFlo 6000 Mobile Pilot Plant
fermentor equipped with an ML-6100 touch-screen controller and 100 L working volurne vessel, (all equipment manufactured
by New Brunswick Scientific, Edison, NJ). NBS' proprietary AFS-BioCommand software was used to control a multi-loop
cascade strategy, wherein each of four process parameters were altered in sequence so as to maintain the desired D.O. level.
Capable of managing up to eight fermentors, bioreactors, or ancillary instruments, this software automates the tedious and
error-prone jobs of logging data, computing real and derived process values, and altering setpoints on the basis of time or
metabolic events. In this study, AFS-BioCommand was programmed to maintain a D.O. level of 30% of air saturation by
automatically increasing agitation rates from 200 to 450 rpm, then vessel pressure from 0.35 to 0.75 bar, aeration rate from 0.5
to 1 VVM and simultaneously shifting temperature from 28C to 25C, when D.O. fell below its setpoint. Based on optimization
studies conducted on the bench level, pH was maintained between 6.2 and 6.8. A deadband was easily configured by using
the local controller for the low setpoint and the supervisory control software for the high setpoint.
Utilizing the multi-loop cascade strategy provided several benefits. First and foremost, D.O.
was able to be maintained at optimal rates for production of rapamycin, a feat unable to be
accomplished using a single loop control strategy ( see figure ). Agitation rates could
also be significantly reduced, to minimize shear forces and enable higher yields of both
cells and secondary metabolites.
Temperature was also lowered from that optimal for culture growth to the optimal range for
rapamycin production. The lower temperature had the side benefit of slowing cell growth,
thereby decreasing oxygen demands, which hPage: All 1 2 3 Related biology technology :1
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