| Summary: | Mammalian cell perfusion cultures require practical and efficient cell retention devices
that maintain high performance while minimizing negative influences on the culture. The
acoustic separator is a mechanically simple device that provides high separation
efficiency for months of continuous operation. The cells are retained in the chamber by
acoustic forces whose magnitude is limited because the acoustic energy is ultimately
dissipated as heat. On the other hand, the cell suspension, pumped into the acoustic
separator through a recirculation line, is cooled somewhat by heat transfer to the ambient
environment. Thus, the thermal control of the acoustic filter is essential to avoid negative
effects on the cell culture while maximizing efficient separation.
The purpose of this work was to investigate the thermal aspects of acoustic separations.
Cell culture experiments demonstrated that CHO cells could be exposed to a cyclic
temperature variation from 31.5 to 38.5°C, in a simulated acoustic separator environment,
without significant effects on their growth rate, glucose consumption or t-PA production.
Following an investigation of the acoustic separator recommended settings, a minimal
recirculation flow rate of 15 L day⁻¹, at an ambient temperature of 22°C with a 45 s run
time was found to provide efficient operation with limited environmental influences on
the cells. Nonetheless, for a reactor cell concentration of 107 cells mL⁻¹ and a 5L day⁻¹
harvest flow rate, the separation efficiency was greater than 95% for ambient
temperatures from 19 to 26°C. Air cooling flow rates from 0 to 16 L min⁻¹ did not
perturb the separation efficiency of the system though air cooling was required to limit
the temperature increase. A central composite factorial design experiment was used to
obtain surface response models of the inlet and outlet temperatures as well as the inlet to
outlet temperature change. These empirical models provided a tool to help optimize
acoustic separator operation (i.e., selecting conditions that ensure temperatures are
maintained in the acceptable range). Also, a theoretical model of the acoustic separator
was developed, based on energy conservation, which provided an estimate of the 3-
dimensional temperature distribution in the device. Once all of the unknown parameters
had been determined by fitting the model to measured temperature data, it was able to
predict the outlet temperatures to within 1°C. It was estimated that 56% of the power
input was transformed into heat in the liquid compared with 6.5% in the transducer wall
and 2% in the reflector wall. It was assumed that the remainder was lost due to the
conversion of electric to acoustic energy and to conduction and eventual dissipation to
the surroundings through the other solid components of the separator. Temperature
profiles generated by the model as well as experimental measurements confirmed that the
air cooling device was essential to control the temperature in the acceptable range. === Applied Science, Faculty of === Chemical and Biological Engineering, Department of === Graduate
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