Hollow fiber bioreactor culture system and method

Chemistry: molecular biology and microbiology – Spore forming or isolating process

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435 3, 435289, 435813, C12N 500, C12N 306

Patent

active

049992988

ABSTRACT:
The cell culturing system of the present invention includes a tubular membrane, e.g. hollow fiber, cartridge. Provision is made for the continuous circulation of a nutrient-containing medium through the tube side of the cartridge by pumping the nutrient-containing medium in an endless loop. The cells to be cultured are placed within the cartridge on the shell side where the desired extracellular products are accumulated. Nutrients are assimilated into the cell culture through the semipermeable tubular membranes and waste products are removed by passing through the semipermeable membranes into the recirculating nutrient-containing medium. Within the endless loop are located a circulating pump, an oxygenator and a pH probe. The system additionally includes a variable delivery feed pump for continuously injecting fresh nutrient-containing solution into the loop, which feed pump is operated at a rate responsive to the measured pH. A portion of the stream exiting the cartridge is continuously split off at a rate identical to that for the introduction for fresh nutrient-containing solution in order to maintain cellular waste products at a suitably low level. The conventional nutrient-solution preparation reservoir has been eliminated from the loop in order to simplify the system and reduce the potential points of entry for contaminating microorganisms. The membrane cartridge is mounted with its longitudinal axis at approximately 60.degree. with respect to the horizontal.

REFERENCES:
patent: 3883393 (1975-05-01), Knazek et al.
patent: 3997396 (1976-12-01), Delente
patent: 4220725 (1980-09-01), Knazek et al.
patent: 4225671 (1980-09-01), Puchinger et al.
"Disinfection, Sterilization, and Preservation", 3d ed., Seymour S. Block (1983), pp. 133 & 135.
"Perry's Chemical Engineer's Handbook", 6th ed., Perry, R. H. and Green, D. W. (1984), pp. 6-62.
"Hollow Fiber Cell Culture", W. R. Grace & Co., Publication No. 535, Jan. 1986.

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