Culture device and method
DCFirst Claim
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1. A culturing system, comprising:
- (a) a medium reservoir for containing a growth medium, and having inlet and outlet ports;
(b) a mass transfer device having first and second ends, said mass transfer device being selected from the group consisting of hollow fiber mass transfer devices and stacked plate filters;
(c) a pump including inlet and discharge ports for pumping the growth medium from the medium reservoir to the mass transfer device;
(d) a sterile barrier tangential flow membrane device connected to the mass transfer device, said sterile barrier tangential flow membrane device being selected from the group consisting of hollow fiber mass transfer devices and stacked plate filters;
(e) means for harvesting microorganisms grown in the mass transfer device, such harvesting means being selectively openably and closably coupled with the mass transfer device;
(f) medium flow control means comprising flow ports designated A, B, C, and D for connecting;
(i) in a first configuration, port A in flow communication with B, and port C in flow communication with port D; and
(ii) in a second configuration, port A in flow communication with port D, and port B in flow communication with port C; and
(g) conduits connecting the pump discharge port to port C, the pump inlet to the reservoir outlet port, the reservoir inlet port to port A, the mass transfer device first end to the port B and the mass transfer device second end to port D.
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Abstract
A culturing system and method particularly useful for producing cellular products such as viral pathogens of cells. It includes a mass transfer culture segment, stacked filter plates to adjust the medium composition, and a product removal and concentration segment. The mass transfer culture segment utilizes changed directional flow of the medium to maximize cell growth and production of product. The stacked filter plates allow addition of sterile fresh medium and removal of growth inhibitory substances.
87 Citations
19 Claims
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1. A culturing system, comprising:
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(a) a medium reservoir for containing a growth medium, and having inlet and outlet ports; (b) a mass transfer device having first and second ends, said mass transfer device being selected from the group consisting of hollow fiber mass transfer devices and stacked plate filters; (c) a pump including inlet and discharge ports for pumping the growth medium from the medium reservoir to the mass transfer device; (d) a sterile barrier tangential flow membrane device connected to the mass transfer device, said sterile barrier tangential flow membrane device being selected from the group consisting of hollow fiber mass transfer devices and stacked plate filters; (e) means for harvesting microorganisms grown in the mass transfer device, such harvesting means being selectively openably and closably coupled with the mass transfer device; (f) medium flow control means comprising flow ports designated A, B, C, and D for connecting; (i) in a first configuration, port A in flow communication with B, and port C in flow communication with port D; and (ii) in a second configuration, port A in flow communication with port D, and port B in flow communication with port C; and (g) conduits connecting the pump discharge port to port C, the pump inlet to the reservoir outlet port, the reservoir inlet port to port A, the mass transfer device first end to the port B and the mass transfer device second end to port D. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10)
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11. A method of culturing microorganisms in a closed culturing system to obtain a desired product, comprising the steps of:
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(a) providing a mass transfer culturing system comprising; (i) a reservoir having inlet and outlet ports; (ii) a pump having inlet and discharge ports; (iii) a mass transfer device with first and second ends, said mass transfer device being selected from the group consisting of hollow fiber mass transfer devices and stacked plate filters; and (iv) flow control means comprising flow ports designated A, B, C, and D, for connecting; (A) in a first configuration, port A in flow communication with port B, and port C in flow communication with port D; and (B) in a second configuration, port A in flow communication with port D, and port B in flow communication with port C; and (v) conduits connecting the pump discharge port to port C, the pump inlet to the reservoir outlet port, the reservoir inlet port to port A, the mass transfer device first end to port B, and the mass transfer device second end to port D; (b) providing in the mass transfer device an inoculum of cells capable of producing a desired product; (c) flowing a medium from the reservoir through the mass transfer device to expose the cells thereto; (d) periodically switching the flow control means between the respective first and second configurations to periodically reverse the flow of medium through the mass transfer device; (e) adjusting the composition of the medium to obtain production of the desired product, by means of a sterile barrier tangential flow membrane device selected from the group consisting of hollow fiber mass transfer devices and stacked plate filters; and (f) filtratingly concentrating the desired product produced by the cells in the closed culturing system. - View Dependent Claims (12, 13, 14, 15, 16, 17)
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18. A culturing system comprising:
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(a) a tangential flow growth device for growing a cell culture, said tangential flow growth device being selected from the group consisting of hollow fiber mass transfer devices and stacked plate filters; (b) a flow circuit coupled to the tangential flow growth device for selectively reversibly flowing a cell growth medium therethrough in one of selected opposite flow directions, said flow circuit comprising; (i) a cell growth medium reservoir; (ii) a pump; (iii) a four-way valve; and (iv) a sterile barrier tangential flow membrane device selected from the group consisting of hollow fiber mass transfer devices and stacked plate filters, wherein the flow circuit is constructed and arranged to flow cell growth medium through the tangential flow growth device in one of two selected opposite flow directions; (c) an auxiliary flow circuit comprising an auxiliary reversible pump, joined to the tangential flow growth device and arranged for flowing cell culture from the tangential flow growth device through the auxiliary circuit for recirculation thereof; and (d) means for concentrating the cells in cell culture which is withdrawn from the tangential flow growth device, comprising an ultrafiltration means.
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19. A culturing system, comprising:
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(a) a tangential flow growth device for culturing of a cell culture; (b) a flow circuit including a growth medium reservoir and pump for flowing growth medium through the tangential flow growth device; and (c) a sterile barrier port means coupled to the tangential flow device for sterilely introducing or removing selected material to or from the tangential flow growth device, comprising two valves in series, each of which is independently selectively openable or closable, said valves being contiguous and in closed flow communication with one another, without any flow circuit branches therebetween.
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Specification