Cadence™ Acoustic Separator

Enabling Technology for Continuous Clarification of Batch Cell Culture

The Cadence Acoustic Separator (CAS) enables the continuous removal of CHO cells and cell debris using a Cadence single-use acoustic chamber to achieve clarification of harvested cell culture fluid (HCCF) ready for downstream processing. The acoustophoretic removal is intrinsically scalable and is optimized for the clarification of high density Chinese Hamster Ovary (CHO) cell lines to provide a robust single-use primary clarification solution that delivers quality that is equivalent to centrifugation without the scaling, footprint and cleaning issues common with this solution. The Cadence Acoustic Separator is an easy to use technology without the volume limitations experienced by depth filtration solutions that lead to large footprint and buffer consumption or the need for process additives to enhance the performance.

  • Optimized for high CHO cell densities in the range 20 - 50 x 106 cells/mL
  •  Performance scales directly from process development to full scale processes
  • Quality of HCCF unaffected and comparable to centrifugation
  • Small footprint compared to equivalent centrifugation or depth filter solutions
  • Reduced depth filtration requirement for secondary polishing
  •  Lower buffer consumption throughout the clarification process
  • Continuous operation to link with continuous downstream purification including chromatography using the Cadence BioSMB PD system

Description

Advances in fed batch cell culture have led to higher cell densities of up to 50 x 106 cells/ml and product titers of > 5g/L. Accompanied by a shift towards the use single-use technology in cell culture there is a drive to improve the efficiency of the cell harvest and clarification stage to generate HCCF for capture chromatography and subsequent downstream processing. This is further driven by the evolution of continuous processes where there is a preference for a continuous feed of HCCF available for direct load to the continuous multicolumn capture chromatography step using the Cadence BioSMB PD system. Existing cell culture clarification using either centrifugation or depth filtration are typically operated in batch mode and require bulk storage of feed or HCCF during the process.

The Cadence Acoustic Separator provides a novel scalable single-use technology for cell culture clarification based on an acoustophoretic separation. Acoustic wave separation (AWS) technology involves the use of low frequency acoustic forces to generate a 3 dimensional standing wave across a flow channel. Cell culture from a fed batch bioreactor enters the flow channel, and as the cells pass through the 3D standing wave they are trapped by the acoustic forces. The trapped cells migrate to the nodes of the standing wave, and begin to clump together till such time as their buoyancy decreases and they settle out of the suspension by gravity.

After separation of cells and cell debris, the permeate from Cadence Acoustic Separator shows a significant reduction in turbidity and reduces the area requirements for secondary clarification using depth filtration and subsequent filtration for bioburden control.