Flux-dependent transmission of supercoiled plasmid DNA through ultrafiltration membranes

Latulippe, David R.; Ager, Kimberly; Zydney, Andrew L.

doi:10.1016/j.memsci.2007.02.033

Cited by 73 publications

(102 citation statements)

References 28 publications

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“…The sieving coefficients for the supercoiled isoform were approximately half-way between that of the linear and open-circular isoforms. Note that the mean pore size of the 100 kDa membrane (approximately 6 nm as determined from hydraulic permeability and dextran sieving measurements [6]) was well over an order of magnitude smaller than the radii of gyration for all three plasmid isoforms. These results clearly demonstrate that the different rates of plasmid transmission during UF were not due to differences in the size of the different plasmid isoforms.…”

Section: Ultrafiltration Of Individual Isoformsmentioning

confidence: 91%

“…Filtrate samples were collected after filtration of at least 1 mL to wash out the dead-volume beneath the membrane. Additional details on the ultrafiltration experiments are provided elsewhere [6].…”

Section: Ultrafiltrationmentioning

confidence: 99%

“…Recent studies by Latulippe and Zydney [6,7] have demonstrated that transmission of supercoiled plasmid DNA through small pore ultrafiltration (UF) membranes occurs by elongation of the plasmid in the highly converging flow field that forms above the membrane pores -this phenomenon is shown schematically in Fig. 1.…”

Section: Introductionmentioning

confidence: 99%

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Separation of plasmid DNA isoforms by highly converging flow through small membrane pores

Latulippe¹,

Zydney²

2011

Journal of Colloid and Interface Science

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Section: Ultrafiltration Of Individual Isoformsmentioning

confidence: 91%

Section: Ultrafiltrationmentioning

confidence: 99%

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Separation of plasmid DNA isoforms by highly converging flow through small membrane pores

Latulippe¹,

Zydney²

2011

Journal of Colloid and Interface Science

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“…These systems may not only provide lower cost of production, they would also eliminate the need to develop and validate cleaning cycles. Membrane systems may also be attractive in the downstream processing of second-generation biotherapeutics, including protein-polymer conjugates (Molek and Zydney, 2007), plasmid DNA for gene therapy applications and DNA-based vaccines (Latulippe et al, 2007), and virus particles (Grzenia et al, 2008). The successful development of new membrane processes targeted for these diverse applications will be built upon recent, and future, progress in understanding the fundamental phenomena governing protein transport and fouling during membrane filtration.…”

Section: Discussionmentioning

confidence: 99%

Membrane technology for purification of therapeutic proteins

Zydney

2009

Biotech & Bioengineering

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Membrane systems are used throughout the downstream purification in the commercial production of high value therapeutic proteins. Over the last two decades, new membranes, modules, and systems have been developed specifically to meet the requirements of the biotechnology industry. These developments have been facilitated by an improved fundamental understanding of: (1) the effects of electrostatic interactions and concentration polarization on protein transmission during ultrafiltration and (2) the role of membrane morphology on protein fouling during both sterile and virus filtration. This perspective highlights some of the key work in this area and provides insights into possible future improvements in membrane technology for the purification of recombinant therapeutic proteins.

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“…The actual sieving coefficient, S a , can be evaluated from the observed sieving coefficient (S o ), filtrate flux (J), and mass transfer coefficient (k) using the stagnant film model (Latulippe et al, 2007).…”

Section: Detergent Transmission During Ultrafiltration Can Be Maximizmentioning

confidence: 99%

Concentrating membrane proteins using ultrafiltration without concentrating detergents

Feroz

Vandervelden

Ikwuagwu

et al. 2016

Biotech & Bioengineering

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Membrane proteins (MPs) are of rapidly growing interest in the design of pharmaceutical products, novel sensors, and synthetic membranes. Ultrafiltration (UF) using commercially available centrifugal concentrators is typically employed for laboratory-scale concentration of low-yield MPs, but its use is accompanied by a concomitant increase in concentration of detergent micelles. We present a detailed analysis of the hydrodynamic processes that control detergent passage during ultrafiltration of MPs and propose methods to optimize detergent passage during protein concentration in larger-scale membrane processes. Experiments were conducted using nonionic detergents, octyl-β-D glucoside (OG), and decyl-β-D maltoside (DM) with the bacterial water channel protein, Aquaporin Z (AqpZ) and the light driven chloride pump, halorhodopsin (HR), respectively. The observed sieving coefficient (So ), a measure of detergent passage, was evaluated in both stirred cell and centrifugal systems. So for DM and OG increased with increasing filtrate flux and decreasing shear rates in the stirred cell, that is, with increasing concentration polarization (CP). Similar effects were observed during filtration of MP-detergent (MPD) micelles. However, lower transmission was observed in the centrifugal system for both detergent and MPD systems. This is attributed to free convection-induced shear and hence reduced CP along the membrane surface during centrifugal UF. Thus to concentrate MPs without retention of detergent, design of UF systems that promote CP is required. Biotechnol. Bioeng. 2016;113: 2122-2130. © 2016 Wiley Periodicals, Inc.

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Flux-dependent transmission of supercoiled plasmid DNA through ultrafiltration membranes

Cited by 73 publications

References 28 publications

Separation of plasmid DNA isoforms by highly converging flow through small membrane pores

Separation of plasmid DNA isoforms by highly converging flow through small membrane pores

Membrane technology for purification of therapeutic proteins

Concentrating membrane proteins using ultrafiltration without concentrating detergents

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