Scale-Up of Ultrasonic Resonance Field Cell Separation Devices Used in Animal Cell Technology

Abstract

Ultrasonic standing waves have been used for the separation of suspended particles, such as animal cells (Kilburn et al., 1989). This technology can be used for cell retention within the fermenter for high density cell culture or as cell removal step in downstream processing. Devices for bench scale applications have been developed and evaluated in experimental set-ups and on laboratory fermenters (Trampler et al., Doblhoff et al., 1994). To scale-up this promising technology for industrial processes, a number of criteria, such as aseptic and hygienic design, steam sterilisability, sufficient flow rates and separation efficiency have to be taken into account. In this paper we will discuss the theoretic limitations of different resonator designs and will describe experimental results with a new type of resonator with an internal cooling loop. The modular, aseptic device is mounted on top of the fermentation equipment and can be steam sterilised in-situ. High amplitudes necessary to achieve separation of animal cells cause thermal and acoustic flow within the separation chamber. The internal cooling loop reduces this temperature increase and thus disrupting forces, which would otherwise limit the achievable flow rate and separation efficiency.