Application Note

S.U.B. Enhancements For High-Density Perfusion Cultures

Source: Thermo Fisher Scientific

Design improvements, performance characterization, modeling, and cell culture

Improvements in single-use systems have allowed implementation of high-density cultures in emerging bioprocess workflows, while progressive advances in media optimization and improved clone genetic selection have underscored the perceived performance limitations of single-use bioreactors (S.U.B.s). This study presents how strategic enhancements to the sparge and agitation systems of Thermo Scientific™ HyPerforma™ S.U.B.s have revealed the potential for a three- to four-fold improvement in mixing and mass transfer performance compared to legacy S.U.B. designs. This study investigates the following:

  • Bioreactor characterization, Thermo Scientific™ TruBio™ DeltaV™ controller optimization, online process analytics, and scalability analysis of the S.U.B. when targeting perfusion applications in working volumes for pilot scale (50 L) to production scale (500 L).
  • High-density culture results (>260 x 106 cells/mL) while maintaining proper operating parameters. New data reveal how a 50 L S.U.B. equipped with a specialized precision drilled-hole sparger (DHS), single-use foam probe, and oversized impeller is able to improve overall S.U.B. operating efficiency. Results also include specific suggestions on how to maintain a nearly ideal dissolved carbon dioxide environment, reduce generation of foam in the  eadspace, and produce lower overall shear levels, thus yielding excellent cell viability.