While TFF has been used to remove casein from milk for cheese production for over 35 years, and in pharmaceutical manufacture of biotherapeutic proteins for 20 years, the rapid decline in filtration rate (i.e., flux) at high protein concentrations is a limitation that still needs to be addressed. This is particularly important for mAbs, many of which are 140–160 kDa immunoglobulin G (IgG) type proteins recovered at concentrations of 200 mg/mL or higher. This work reports the direct measurement of local transmembrane pressure drops and off-line confocal imaging of protein accumulation in stagnant regions on the surface of a 30 kDa regenerated cellulose membrane in a flat-sheet configuration widely used in manufacture of biotherapeutic proteins. These first-of-a-kind measurements at the membrane surface show a 50 μm thick protein layer is uniformly deposited when protein concentration exceeds 200 mg/mL. The localized measurements confirm the role of protein deposition on limiting ultrafiltration rate and indicate possible targets for improving membrane performance.

F. Cunha, Zuponcic, J., Rossi, F., Springer, G., Ximenes, E., Bruns, N., Moomaw, J. F., Bowes, B. D., Qian, K. K., Yu, Z., Yang, D., Corvari, V. J., Ardekani, A., Reklaitis, G., Ladisch, M., Intramodule pressure profiles and protein accumulation during tangential flow filtration, Biotechnol. Prog. 2023; e3389. https://doi.org/10.1002/btpr.3389

Contamination in food samples is usually detected by PCR analysis after an aqueous enrichment step. Because bacteria which enter a viable but non-culturable state cannot be concentrated by enrichment of food samples, we have developed a strategy for concentration of bacteria from aqueous samples using tangential flow filtration with single hollow fiber membranes.

Previous attempts were hindered by high losses of bacteria to the filtration system. Here, the research goal was to maximize the recovery of E. coli from hollow fiber filters while also maximizing flux, which contributed to keep the filtration time low. We observed that high shear rates, up to 27,000 1/s, resulted in lower attachment of bacteria to membrane surfaces and increased the bacterial recovery caused by increased convection to the filter at high flux conditions. Investigation of the bacterial concentration in a wide range of flux conditions revealed that the main cause of bacterial losses was due to its accumulation on the membrane surface. Recoveries near 90% were achievable at high shear rates when flux was ≤ 300 L. m-2.h-1.

Zuponcic, J., Cunha, F., Springer, G., Ximenes, E., Ladisch, M. Effect of flux and shear rate on E. coli recovery in tangential flow filtration through a single hollow fiber. Biotechnol. Prog. 2024; 40(3):e3432. doi: 10.1002/btpr.3432.