Clarification of Cell Harvests from Micro Bioreactors

Lab scale clarification of cell harvests is increasingly becoming more challenging as the standard clarification techniques such as centrifugation, tangential flow filtration (TFF) and depth filtration are not easily adaptable to micro bioreactors which require multiple processing of small volumes of cell harvests, typically 50 mL. Centrifugation may damage the shear sensitive mammalian cells and not only release undesirable intra cellular proteins and DNA into the broth but also submicron particles which are difficult to remove. TFF systems require long setup time and are prohibitively expensive for lab scale volumes. Depth filters on the other hand necessitate monitoring of differential pressures and sometimes allow passage of cell debris and other fine particulate which tend to choke the downstream 0.2µm sterilizing grade filters. Also, these require large pre-use flush volumes to remove inherent extractables owing to their cellulosic matrix with inorganic filter aids such as diatomaceous earth or perlite.

In addition to the above limitations, all the mentioned steps also require downstream secondary clarification to retain finer contaminants. This involves high retention depth filters in series with final membrane filtration, resulting in a multi-step cumbersome process involving pumps, tubing, multiple connections and collection vessels, requiring high manpower and extended process time. These issues demand a faster, cost effective and reliable method for primary as well as secondary clarification in the lab.

Mini Harvester Funnels
Highly efficient, miniaturized multilayered, vacuum filtration devices for parallel processing of multiple cell harvests from micro-bioreactors have been developed.

These are designed to offer primary and secondary clarification of up to 50 mL of mammalian cell culture within minutes. These devices house a large filtration area pleated cartridge filter built into the funnel tube which fits on the neck of the receiver tube for clarification of high density cell cultures.

Primary Clarification of CHO cell harvest with Harvester Mini Funnel

0.2 Filtration after Primary Clarification with Harvester Mini Funnel

Clarification of Cell Harvests from Micro Bioreactors