US 11,999,937 B2
Foam mitigation in bioreactors using ultrasound
Gregory Bremer, Jr., New York, NY (US)
Assigned to Sartorius Stedim North America Inc., Bohemia, NY (US)
Filed by Sartorius Stedim North America Inc., Bohemia, NY (US)
Filed on Oct. 16, 2018, as Appl. No. 16/161,382.
Prior Publication US 2020/0115669 A1, Apr. 16, 2020
Int. Cl. C12M 3/00 (2006.01); C12M 1/00 (2006.01); C12M 1/04 (2006.01); C12M 1/21 (2006.01); C12M 1/10 (2006.01)
CPC C12M 41/02 (2013.01) [C12M 1/04 (2013.01); C12M 23/28 (2013.01); C12M 1/10 (2013.01)] 17 Claims
OG exemplary drawing
 
1. A bioreactor for culturing of microorganisms or cells and for mitigating the accumulation of foam within the bioreactor via ultrasound and without the use of direct mechanical agitation, the bioreactor comprising:
a casing defining an interior space of the bioreactor, the casing extending between a first, lower end and a second, upper end and including an intended filling height located between the first end and the second end, wherein said interior space is configured to receive and hold a culture medium with microbial or cellular liquid cultures between the lower end and the intended filling height; and
at least one coupling element provided on the casing at a location between the intended filling height and the upper end, the coupling element adapted to receive a foam mitigation device external to the casing, the foam mitigation device being configured to emit ultrasonic waves for mitigation of foam built-up in the interior space of the bioreactor during use of the bioreactor for culturing of microorganisms or cells;
wherein the coupling element further includes a portion of the casing that is substantially transmissive to ultrasound waves and is configured to allow ultrasonic waves generated by the foam mitigation device act upon foam built-up in the interior space of the bioreactor.
 
7. A system for culturing of microorganisms or cells comprising:
a bioreactor for culturing of microorganisms or cells and for mitigating the accumulation of foam within the bioreactor via ultrasound and without the use of direct mechanical agitation, the bioreactor comprising:
a casing defining an interior space of the bioreactor, the casing extending between a first, lower end and a second, upper end and including an intended filling height located between the first end and the second end, the casing including at least a portion that is substantially transmissive to ultrasound waves, and wherein said interior space is configured to receive and hold a culture medium with microbial or cellular liquid cultures;
at least one inlet port for introducing gases and/or liquids into the interior space of the bioreactor;
at least one outlet port for exhausting gases and/or removing liquids from the interior space of the bioreactor; and
a foam mitigation device comprising an ultrasonic wave generator for generating ultrasonic waves, the foam mitigation device provided external to the casing and such that it is configured to transmit ultrasonic waves through a wall of the casing at a location between the intended filling height and the upper end, wherein said ultrasonic waves are configured to act upon foam built-up in the interior space of the bioreactor during use of the bioreactor for culturing of microorganisms or cells.
 
15. A method of foam mitigation in bioreactors for culturing of microorganisms or cells comprising the steps of:
culturing of microorganisms or cells in a casing of a bioreactor, wherein the casing of the bioreactor comprises at least one ultrasonically transmissive part being configured to allow ultrasonic waves to enter the interior of the bioreactor; and
generating ultrasonic waves via an ultrasonic wave generator mounted external to the casing at a location between a fill height of a culture medium and an upper end of the casing, wherein the ultrasonic waves have a main direction of propagation that extends through the at least one ultrasonically transmissive part and at an angle that is oriented away from the upper end of the casing and such that the and pointing said ultrasonic waves are directed toward foam built-up inside the bioreactor.