Steven R. Pearl

High performance tangential flow filtration

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.

A new coiled hollow-fiber module design for enhanced microfiltration performance in biotechnology

The microfiltration performance of a novel membrane module design with helically wound hollow fibers is compared with that obtained with a standard commercial-type crossflow module containing linear hollow fibers. Cell suspensions (yeast, E. coli, and mammalian cell cultures) commonly clarified in the biotechnology industry are used for this comparison. The effect of variables such as transmembrane pressure, particle suspension concentration, and feed flow rate on membrane performance is evaluated. Normalized permeation fluxes versus flow rate or Dean number behave according to a heat transfer correlation obtained with centrifugal instabilities of the Taylor type. The microfiltration performance of this new module design, which uses secondary flows in helical tubes, is significantly better than an equivalent current commercial crossflow module when filtering suspensions relevant to the biotechnology industry. Flux and capacity improvements of up to 3.2-fold (constant transmembrane pressure operation) and 3.9-fold (constant flux operation), respectively, were obtained with the helical module over those for the linear module.

A liquid porosimetry technique for correlating intrinsic protein sieving: Applications in ultrafiltration processes

Abstract The understanding of variation in sieving properties of membranes is of great importance for the successful development of ultrafiltration applications. A liquid porosimetry technique is presented to quantify the sieving variation among several polyethersulfone ultrafiltration membranes. Observed sieving coefficients were measured with proper precautions taken to control and minimize fouling. These data were translated to intrinsic sieving coefficients using a stagnant film model. The intrinsic membrane sieving coefficient correlated well with the liquid porosimetry data. This liquid porosimetry technique can distinguish between membranes of different molecular weight cut-off and is sensitive enough to capture slight changes in the sieving coefficient of variants of the same cut-off membrane. This technique has several attractive features: it is non-destructive, independent of the module configuration and relatively simple to perform. Two potential applications of this technique are also examined: (1) quantification of the effect of membrane variation on high performance tangential flow filtration (HPTFF) for protein separations and (2) development of a membrane integrity test to ensure batch-to-batch consistency. This technique has the potential for use in membrane quality control, membrane selection, and validation of industrial ultrafiltration processes.