Bioreactor With Higher Agitation Rates

Patent metadata

Field	Value
Publication number	US-2018010082-A1
Application number	US-201715712302-A
Country	US
Kind code	A1
Filing date	Sep 22, 2017
Priority date	Jun 3, 2016
Publication date	Jan 11, 2018
Grant date	—

Abstract

A single-use bioreactor is provided. The single-use bioreactor may include a bioprocess container, a shell, at least one agitator, at least one sparger, at least one gas filter inlet port for the sparger(s) and headspace overlay, at least one fill port, at least one harvest port, at least one sample port, and at least one probe. In examples, at least one controller may monitor and control one or more parameters associated with the single-use bioreactor A method to cultivate and propagate mammalian cells is also provided. The method may include cultivating under suitable conditions and in a suitable culture medium in a first single-use bioreactor, transferring the medium containing the cells obtained by propagation from the at least one mammalian cell is into a second single-use bioreactor, transferring the medium containing the cells obtained by propagation from the at least one mammalian cell is into a third single-use bioreactor, and cultivating the cells in the third bioreactor.

First claim

1 . A bioreactor comprising:
a bioprocess container having a top, a bottom, and at least one side wall therebetween, the bioprocess container defining a hollow enclosure for receiving a culture medium; a mixing device comprising a rotatable shaft coupled to at least one impeller; and a motor coupled to the rotatable shaft for rotating the shaft and the at least one impeller, the motor being configured to rotate the impeller at a rate of from 80 rpm to 200 rpm.

2 . A bioreactor as defined in claim 1 , wherein the mixing device comprises at least one top impeller and at least one bottom impeller that extend into the hollow enclosure of the bioprocess container.

3 . A bioreactor as defined in claim 2 , wherein the top impeller and the bottom impeller are made from a polymer material, the top impeller and the bottom impeller having a hydrophilic surface.

4 . A bioreactor as defined in claim 1 , further comprising at least one baffle being configured to extend adjacent to the side wall of the bioprocess container in a longitudinal direction, the baffle having a shape that extends radially inward from the side wall in an amount sufficient to affect fluid flow in the hollow enclosure during mixing of a culture medium by the mixing device.

5 . A bioreactor as defined in claim 1 , wherein the bioprocess container is made from a liquid impermeable and flexible shape-conforming material comprising a polymer film.

6 . A bioreactor comprising:
a bioprocess container having a top, a bottom, and at least one side wall therebetween, the bioprocess container defining a hollow enclosure for receiving a culture medium; a mixing device comprising a rotatable shaft coupled to at least one impeller; and a motor coupled to the rotatable shaft for rotating the shaft and the at least one impeller, the motor being configured to rotate the at least one impeller so as to impart into a culture medium contained within the bioprocess chamber a power per unit volume of greater than about 38 W/m 3 .

7 . A bioreactor as defined in claim 6 , wherein the motor is configured to rotate the impeller so as to impart into a culture medium contained within the bioprocess container of a power per unit volume of from about 40 W/m 3 to about 300 W/m 3 .

8 . A bioreactor as defined in claim 6 , wherein the motor is configured to rotate the impeller so as to impart into a culture medium contained within the bioprocess container a power per unit volume of from about 55 W/m 3 to about 150 W/m 3 .

9 . A bioreactor as defined in claim 6 , wherein the mixing device comprises at least one top impeller and at least one bottom impeller that extend into the hollow enclosure of the bioprocess container.

10 . A bioreactor as defined in claim 9 , wherein the top impeller and the bottom impeller are made from a polymer material, the top impeller and the bottom impeller having a hydrophilic surface.

11 . A bioreactor as defined in claim 6 , further comprising at least one baffle being configured to extend adjacent to the side wall of the bioprocess container in a longitudinal direction, the baffle having a shape that extends radially inward from the side wall in an amount sufficient to affect fluid flow in the hollow enclosure during mixing of a culture medium by the mixing device.

12 . A bioreactor as defined in claim 6 , wherein the bioprocess container is made from a liquid impermeable and flexible shape-conforming material comprising a polymer film.

13 . A bioreactor as defined in claim 6 , further comprising a controller in communication with the motor, the controller being configured to control the motor so that the at least one impeller rotates at a rate sufficient to impact into a culture medium a power per unit volume of greater than about 38 W/m 3 .

14 . A bioreactor as defined in claim 13 , further comprising at least one sparger that releases a sparge gas into the bioprocess container, the sparger being in communication with the controller, the controller being configured to control the sparger so that the sparge rate to the bioprocess container is at a superficial gas velocity of less than about 8.0×10 −4 m/s.

15 . A method for propagating a cell culture comprising:
adding a cell culture in a fluid medium into a bioprocess container, the bioprocess container having a top, a bottom, and at least one side wall therebetween, the bioprocess container defining a hollow enclosure for receiving the cell culture; and mixing the fluid medium containing the cell culture, the fluid medium being mixed by delivering a mixing energy in power per unit volume to the fluid medium at a rate greater than about 38 W/m 3 .

16 . A method as defined in claim 15 , wherein the fluid medium is mixed by delivering a mixing energy to the fluid medium at a rate of from about 40 W/m 3 to about 300 W/m 3 .

17 . A method as defined in claim 15 , wherein the fluid medium is mixed by delivering a mixing energy to the fluid medium at a rate of from about 55 W/m 3 to about 150 W/m 3 .

18 . A method as defined in claim 15 , wherein the fluid medium is mixed by rotating an impeller within the bioprocess container, the impeller being rotated at a rate of greater than about 80 rpm.

19 . A method as defined in claim 18 , wherein the fluid medium is mixed by rotating two impellers within the bioprocess container, the two impellers being spaced apart along a rotating axis.

20 . A method as defined in claim 18 , wherein the at least one impeller is rotated at a rate of from about 90 rpm to about 100 rpm.

21 . A method as defined in claim 15 , wherein the fluid medium is mixed in a manner such that a volumetric oxygen mass transfer coefficient is increased by greater than 30% in comparison to an identical bioreactor containing an identical fluid medium in which the fluid medium is mixed at a rate of 24 W/m 3 .

22 . A method as defined in claim 15 , wherein the fluid medium is mixed without substantial foam formation.

23 . A method as defined in claim 15 , further comprising the step of feeding a sparge gas into the fluid medium while the fluid medium is being mixed, the sparge gas being fed to the bioprocess container at a superficial gas velocity of less than about 8.0×10 −4 m/s

24 . A method as defined in claim 15 , wherein the bioprocess container is made from a liquid impermeable flexible film.

25 . A method as defined in claim 24 , wherein the fluid medium is mixed by a top impeller spaced from a bottom impeller along a rotatable shaft extending into the hollow enclosure of the bioprocess container, the top impeller and the bottom impeller both being made from a polymer material.

Assignees

• Lonza Ag

Inventors

• Jaques Colin Mark
• Khan Mohsan Waseem
• Costa Rita D'Ornelas P De Barros
• Beaney Anthony
• Valentine David

Classifications

• B01F2215/0073

  Operations & Transport · mapped topic

• C12M1/02

  with agitation means; with heat exchange means · CPC title

• C12M23/28

  disposable or single use · CPC title

• C12M27/20 Primary

  Baffles; Ribs; Ribbons; Auger vanes · CPC title

• B01F35/513

  Flexible receptacles, e.g. bags supported by rigid containers · CPC title