Tangential flow filtration is advantageous for bioreactor clarification as the permeate stream could be introduced directly to the subsequent product capture step. However, membrane fouling coupled with high product rejection has limited its use. Here, the performance of a reverse asymmetric hollow fiber membrane where the more open pore structure faces the feed stream and the barrier layer faces the permeate stream has been investigated. The open surface contains pores up to 40 μm in diameter while the tighter barrier layer has an average pore size of 0.4 μm. Filtration of Chinese hamster ovary cell feed streams has been investigated under conditions that could be expected in fed batch operations. The performance of the reverse asymmetric membrane is compared to that of symmetric hollow fiber membranes with nominal pore sizes of 0.2 and 0.65 μm. Laser scanning confocal microscopy was used to observe the locations of particle entrapment. The throughput of the reverse asymmetric membrane is significantly greater than the symmetric membranes. The membrane stabilizes an internal high permeability cake that acts like a depth filter. This stabilized cake can remove particulate matter that would foul the barrier layer if it faced the feed stream. An empirical model has been developed to describe the variation of flux and transmembrane pressure drop during filtration using reverse asymmetric membranes. Our results suggest that using a reverse asymmetric membrane could avoid severe flux decline associated with fouling of the barrier layer during bioreactor clarification.
Membranes have been used extensively for the purification and separation of biological species. A persistent challenge is the purification of species from concentrated feed solutions such as extracellular vesicles (EVs) from biological fluids. Investigated is a new method to isolate micro‐ and nanoscale species termed tangential flow for analyte capture (TFAC), which is an extension of traditional tangential flow filtration. Initially, EV purification from plasma on ultrathin nanomembranes is compared between both normal flow filtration (NFF) and TFAC. NFF results in rapid formation of a protein cake which completely obscures any captured EVs and also prevents further transport across the membrane. On the other hand, TFAC shows capture of CD63 positive small EVs with minimal contamination. The use of TFAC to capture target species over membrane pores, wash, and then release in a physical process that does not rely upon affinity or chemical interactions is explored. This process is studied with model particles on both ultrathin and conventional thickness membranes. Successful capture and release of model particles is observed using both membranes. Ultrathin nanomembranes show higher efficiency of capture and release with significantly lower pressures indicating that ultrathin nanomembranes are well‐suited for TFAC of delicate nanoscale particles such as EVs.
more » « less- Award ID(s):
- 1660177
- NSF-PAR ID:
- 10372418
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Advanced Materials Technologies
- Volume:
- 4
- Issue:
- 11
- ISSN:
- 2365-709X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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