skip to main content

Search for: All records

Creators/Authors contains: "Qian, Xianghong"

Note: When clicking on a Digital Object Identifier (DOI) number, you will be taken to an external site maintained by the publisher. Some full text articles may not yet be available without a charge during the embargo (administrative interval).
What is a DOI Number?

Some links on this page may take you to non-federal websites. Their policies may differ from this site.

  1. Regulatory authorities place stringent guidelines on the removal of contaminants during the manufacture of biopharmaceutical products. Monoclonal antibodies, Fc-fusion proteins, and other mammalian cell-derived biotherapeutics are heterogeneous molecules that are validated based on the production process and not on molecular homogeneity. Validation of clearance of potential contamination by viruses is a major challenge during the downstream purification of these therapeutics. Virus filtration is a single-use, size-based separation process in which the contaminating virus particles are retained while the therapeutic molecules pass through the membrane pores. Virus filtration is routinely used as part of the overall virus clearance strategy. Compromised performance of virus filters due to membrane fouling, low throughput and reduced viral clearance, is of considerable industrial significance and is frequently a major challenge. This review shows how components generated during cell culture, contaminants, and product variants can affect virus filtration of mammalian cell-derived biologics. Cell culture-derived foulants include host cell proteins, proteases, and endotoxins. We also provide mitigation measures for each potential foulant. 
    more » « less
  2. One major challenge in the development of nanoparticle-based therapeutics, including viral vectors for the delivery of gene therapies, is the development of cost-effective purification technologies. The objective of this study was to examine fouling and retention behaviors during the filtration of model nanoparticles through membranes of different pore sizes and the effect of solution conditions. Data were obtained with 30 nm fluorescently labeled polystyrene latex nanoparticles using both cellulosic and polyethersulfone membranes at a constant filtrate flux, and both pressure and nanoparticle transmission were evaluated as a function of cumulative filtrate volume. The addition of NaCl caused a delay in nanoparticle transmission and an increase in fouling. Nanoparticle transmission was also a function of particle hydrophobicity. These results provide important insights into the factors controlling transmission and fouling during nanoparticle filtration as well as a framework for the development of membrane processes for the purification of nanoparticle-based therapeutics. 
    more » « less
  3. Abstract

    Alternating tangential flow filtration (ATF) has become one of the primary methods for cell retention and clarification in perfusion bioreactors. However, membrane fouling can cause product sieving losses that limit the performance of these systems. This study used scanning electron microscopy and energy dispersive X‐ray spectroscopy to identify the nature and location of foulants on 0.2 μm polyethersulfone hollow fiber membranes after use in industrial Chinese hamster ovary cell perfusion bioreactors for monoclonal antibody production. Membrane fouling was dominated by proteinaceous material, primarily host cell proteins along with some monoclonal antibody. Fouling occurred primarily on the lumen surface with much less protein trapped within the depth of the fiber. Protein deposition was also most pronounced near the inlet/exit of the hollow fibers, which are the regions with the greatest flux (and transmembrane pressure) during the cyclical operation of the ATF. These results provide important insights into the underlying phenomena governing the fouling behavior of ATF systems for continuous bioprocessing.

    more » « less
  4. Mixed-matrix electrospun membranes were developed to investigate ammonium removal from low ammonium concentration wastewaters for the first time. Particles derived from the inexpensive zeolite 13X were successfully incorporated into polyethersulfone (PES) matrices. The fabricated mixed-matrix electrospun membranes demonstrate high ammonium removal capacity reaching over 55 mg/gzeolite, more than 2.5 times higher than the previously fabricated mixed-matrix membranes via non-solvent induced phase inversion. Moreover, the membranes fabricated exhibit high permeability and ease of regeneration. Over 90% of total ammonium nitrogen (TAN) can be removed from low TAN wastewaters such as aquaculture wastewaters. In addition to zeolite 13X, other zeolite particles including zeolite Y, zeolite 3A and 4A were also incorporated into the membrane matrix. The inexpensive zeolite 13X show the highest ammonium exchange capacity. Particle type, loading and the level of its dispersion all affect TAN removal capacity. 
    more » « less
  5. null (Ed.)
  6. null (Ed.)
    Copper-based metal–organic frameworks (MOFs) with different oxidation states and near-uniform particle sizes have been successfully synthesized. Mixed-matrix polyimide membranes incorporating 0.1–7 wt% of Cu(II) benzene-1,2,5-tricarboxylic acid (Cu(II)BTC), Cu(I/II)BTC and Cu(I) 1,2-ethanedisulfonic acid (EDS) (Cu(I)EDS) MOFs were fabricated via non-solvent-induced phase inversion process. These membranes are found to be solvent resistant and mechanically stable. Liquid phase nanofiltration experiments were performed to separate toluene from n-heptane at room temperature. These membranes demonstrate preferential adsorption and permeation of the aromatic toluene over aliphatic n-heptane. The amount of MOF particles incorporated, the oxidation state of the Cu ion and membrane, and barrier layer thickness have a significant impact on the separation factor. Toluene/heptane separation factor at 1.47, 1.67 and 1.79 can be obtained for membranes incorporating 7 wt% Cu(II)BTC, Cu(I/II)BTC and Cu(I)EDS respectively at room temperature. 
    more » « less