High performance tangential flow filtration

Robert Van Reis, Shishir Gadam, Leah N. Frautschy, Scott Orlando, Elizabeth M. Goodrich, Skand Saksena, Ralf Kuriyel, Curran M. Simpson, Steven Pearl, Andrew L. Zydney

Research output: Contribution to journalArticlepeer-review

138 Scopus citations


Conventional tangential flow filtration (TFF) has traditionally been limited to separation of solutes that differ by about ten-fold in size. Wide pore-size distributions, membrane fouling, and concentration polarization phenomena have commonly been cited as reasons for this limitation. The use of TFF in the biotechnology industry has therefore been restricted to cell- protein, virus-protein, and protein-buffer separations. A multi-disciplinary team with industrial and academic members was formed to overcome these limitations and enable protein-protein separations using High Performance TFF (HPTFF) systems. Pore-size distributions have been improved with the development of new membrane formulation and casting techniques. Membrane fouling has been controlled by operating in the transmembrane pressure- dependent regime of the filtrate flux curve and by carefully controlling fluid dynamic start-up conditions. Concentration polarization was exploited to enhance, rather than limit, the resolution of solutes. Concentration polarization has also been controlled by operating a co-current filtrate stream that maintains transmembrane pressure constant along the length of the TFF module. High yields and purification factors were obtained even with small differences in protein sieving. IgG-BSA and BSA monomer-oligomer mixtures have successfully been separated with these systems. HPTFF technology provides a competitive purification tool to complement chromatographic processing of proteins.

Original languageEnglish (US)
Pages (from-to)71-82
Number of pages12
JournalBiotechnology and bioengineering
Issue number1
StatePublished - Oct 5 1997

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology


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