ATF System: Perfusion & Cell Retention

The ATF™ System was originally designed for perfusion processes in mammalian cell culture, using hollow fiber filters to achieve an efficient cell separation with low shear and allowing robust large scale manufacturing. The filtration system was taken forward quickly as a preferred cell retention device and now is used in several large scale commercial perfusion facilities to manufacture proteins and antibodies.

The standard bioreactor types of glass in R&D and steel in pilot and production are easy to get an ATF System retrofitted to, with a range of standard adaptors and ports fitting all fermenter suppliers' equipment, including Sartorius /Braun BBI, Applikon, New Brunswick, Bioengineering, Biolafitte/Pierre Guerin etc.

The rapid adoption of single use systems, first as rocker and Wave type systems, then as stirred tank variations both in small rigid plastic configurations and the larger scale bags, required new single use connectors to allow the addition of Refine's cell retention and perfusion device. Connectors such as the Pall Kleenpack, GE's DAC and the Opta from Sartorius Stedim all perform well to achieve this. Today, ATF Systems have been connected to almost every type of single use bioreactor (SUB) from 1L to 1000L volumes: Sartorius Cultibag and STR, XCellerex, Hyclone, GE Wave, ATMI, NBS Celligen Blu and Millipore CellReady.

Refine has been offering several different types of filters for the ATF System for the past 10 years, but recently two versions, a hollow fiber filter at 30-50Kda pore size and a screen module at 70um have proved exceptionally popular: The 30-50Kda ultrafiltration module allows retention of proteins in the bioreactor changing a perfusion process into a concentrated fed-batch process with exceptionally high cell concentrations and yields in a single harvest – suitable for rapid replacement of the standard fed-batch platform.

The 70um screen module is suitable for adherent cells and microcarrier based processes. Vaccine processes, some based upon MDCK or Vero cells, have proved particularly well suited for improvement using the ATF System. In the last few years, the rise of larger scale stem cell culture has shown new process challenges. Stem cells are often grown on microcarriers and can therefore benefit from the ease the ATF System brings to the multiple wash steps and cell-microcarrier separation steps required. Concentration of stem cells can also be performed rapidly with low shear.