Effect of harvesting protocol on performance of a hollow fiber bioreactor

Gramer, Michael J.; Poeschl, Douglas M.; Conroy, Mary Carol; Hammer, Bruce E.

doi:10.1002/(sici)1097-0290(19991105)65:3<334::aid-bit11>3.0.co;2-l

Cited by 21 publications

(15 citation statements)

References 17 publications

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“…The non-cell side medium recirculation rate was initiated at 250 mL/min and was increased up to 600 mL/min according to the bioreactor outlet dissolved oxygen concentration. Cycling was initiated on day 3 with a 70-mL transfer volume and 15-min transfer time (2).…”

Section: Methodsmentioning

confidence: 99%

“…Hollow Fiber System. The Maximizer hollow fiber bioreactor (BioVest International, Inc.) system was run essentially as described (2). A 2.1 m 2 , 10 000 nominal MWCO bioreactor (same fibers as those used in the micro-bioreactor) was used in this study (160-mL cell side volume).…”

Section: Methodsmentioning

confidence: 99%

“…Hollow fiber systems offer a good approach to rapidly produce gram to kilogram quantities of secreted proteins (1)(2)(3). In many cases, good hollow fiber results are achieved by simply using the same medium which was optimized for the cell line in a T-flask.…”

Section: Introductionmentioning

confidence: 99%

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Optimal NS0 Cell Growth in a Hollow Fiber Bioreactor Requires Increased Serum Concentration or a Cholesterol Supplement on the Cell Side of the Fiber

Gramer¹,

Maas²

2003

Biotechnology Progress

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An NSO/GS cell line secreting a humanized antibody was routinely propagated in a T-flask using 2% serum. For scale-up of antibody production, this cell line was inoculated into a hollow fiber system using the same serum concentration. The metabolic activity increased for a few days in the hollow fiber system, but invariably the activity dropped dramatically as the cells died by day 7. A hollow fiber micro-bioreactor was used as a screening tool to examine possible reasons for cell death in the large-scale system. As seen in the hollow fiber system, cells died when 2% serum was used either on the cell side only or on both sides of the fiber in the micro-bioreactor. In contrast, the use of 20% serum on the cell side of the fiber and basal medium on the non-cell side resulted in good cell expansion at high viability. Regardless of the cell side serum concentration, no further growth enhancements were seen when up to 20% serum was placed on the non-cell side of the fiber. These results suggest that a serum component that does not readily cross the fiber is limiting cell growth in the hollow fiber bioreactors. The addition of a cholesterol-rich lipid supplement resulted in better cell growth in the micro-bioreactor, while the addition of other non-cholesterol lipid supplements resulted in no growth enhancement. The growth-enhancing properties of the cholesterol supplement were more pronounced at lower serum concentrations, suggesting that poor growth at low serum concentration was due to suboptimal cholesterol levels. When the cell side serum concentration was increased to 20% in the hollow fiber system, cells grew and filled the bioreactor, allowing a 39-day production run. These results demonstrate that this NSO cell line requires an increased cell side serum concentration for optimal growth and that this requirement is likely due to the inherent cholesterol dependency of this cell line.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Optimal NS0 Cell Growth in a Hollow Fiber Bioreactor Requires Increased Serum Concentration or a Cholesterol Supplement on the Cell Side of the Fiber

Gramer¹,

Maas²

2003

Biotechnology Progress

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“…In this mode of operation, the stirred tank functions as a stirred tank reactor (STR); (ii) the biocatalyst is suspended only within the membrane module, where a biochemical conversion takes place. In the latter case the membrane acts as a medium for biocatalyst segregation; the membrane module functions as a reactor [2]. If the membrane is a medium for encapsulation, enzymes or whole cells are entrapped within semipermeable micro/nano-particles or vesicles such as liposomes [3], polymersomes [4], colloidosomes [5], microgels [6] and polymeric microspheres [7].…”

Section: Role Of Membrane In Biocatalytic Membrane Reactors (Bmrs)mentioning

confidence: 99%

2. Biocatalytic membrane reactors (BMR)

2015

Catalytic Reactors

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“…This operating scheme has been reported as used in several applications, such as: a fixed stratum coupled to a hollowed-fiber module, for extractive fermentation (Dai et al, 2000); a membrane module for antibodies production (Gramer et al, 1999); a system used in protein hydrolysis (Deeslie and Cheryan, 1981); a membrane bioreactor for treatment of phenol-polluted waste waters (Loh et al, 2000); and, production of nutraceutic foods (Sehanputri and Hill, 1999).…”

Section: Assessment Of the Material's Toxicitymentioning

confidence: 99%

06/02425 Aqueous-organic phases separation by membrane reactors in biodesulfurization reactions

Berdugo

Caballero

Godoy

2006

Fuel and Energy Abstracts

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T his work presents a membrane bioreactor prototype used to separate emulsion phases formed in the biodesulfurization reaction. Hydrophobic membranes used for the construction of the prototype allow the separation of the organic/watery phases. The separation unit resembles a tube and carcass heat exchanger. By feeding the emulsion through the housing and due to the pressure gradient pushed on the membrane, the organic phase pass through and allow to obtain an organic phase free of cells and water. Several organic phase/watery phase ratios and many cellular concentrations were evaluated. Results indicate that is possible to separate the phases by manipulating the fluid pressure within the bioreactor. This is possible even for cellular concentrations of the order of 7 g/l . The system can also be used as a reaction unit. The biological conversion was evaluated by verifying the presence of 2-HBP, one of the metabolites of the path 4S in the biodesulfurization reaction. This bioreactor configuration has not been explored before for the biodesulfurization process and therefore it represents an innovation in this research area.En este trabajo se presenta un prototipo de biorreactor de membranas para la separación de las fases de la emulsión formada en la reacción de biodesulfurización. Las membranas hidrofóbicas utilizadas para la construcción del prototipo permiten la separación de las fases acuosa orgánica. La unidad de separación se asemeja a un intercambiador de tubo y coraza. Alimentando la emulsión por la carcasa y gracias al gradiente de presión que se ejerce sobre la membrana, la fase orgánica permea la membrana permitiendo la obtención de la fase orgánica libre de células y agua. Se evaluaron diferentes relaciones fase orgánica/ fase acuosa y diferentes concentraciones celulares. Los resultados indican que es posible separar las fases manipulando la presión del fluido al interior del biorreactor incluso a concentraciones celulares del orden de 7 g/l . El sistema puede ser utilizado también como unidad de reacción, la conversión biológica se evaluó verificando la presencia de 2-HBP, uno de los metabolitos de la ruta 4S en la reacción de Biodesulfurización. Esta configuración de biorreactor no ha sido explorada antes para el proceso de biodesulfurización y por tanto representa una innovación en el área.

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Effect of harvesting protocol on performance of a hollow fiber bioreactor

Cited by 21 publications

References 17 publications

Optimal NS0 Cell Growth in a Hollow Fiber Bioreactor Requires Increased Serum Concentration or a Cholesterol Supplement on the Cell Side of the Fiber

Optimal NS0 Cell Growth in a Hollow Fiber Bioreactor Requires Increased Serum Concentration or a Cholesterol Supplement on the Cell Side of the Fiber

2. Biocatalytic membrane reactors (BMR)

06/02425 Aqueous-organic phases separation by membrane reactors in biodesulfurization reactions

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