Methods and apparatus for gas stream mass transfer with a liquid
A method and system for achieving a gas-liquid mass transfer includes delivering into a compartment of a container a liquid, the liquid having an exposed top surface disposed within the compartment. A stream of a gas is passed over the top surface of the liquid so that the stream of gas produces turbulence on the top surface that is sufficient to achieve the gas-liquid mass transfer. In one embodiment the liquid is a culture that includes cells or microorganisms and the mass transfer functions to oxygenate the culture sufficient to sustain the cells or microorganisms.
1. A method for oxygenating a culture of cells or microorganisms, the method comprising:
a) delivering into a compartment of a container a culture comprised of (i) cells or microorganisms and (ii) medium, the culture having an exposed top surface disposed within the compartment;
b) mixing the culture within the container; and
c) blowing a stream of a gas containing oxygen over at least a portion of the top surface of the culture while the culture is being mixed so that the blowing stream of gas produces turbulence on the top surface that is sufficient to produce a mass transfer of oxygen between the gas and the culture, the mass transfer being sufficient to oxygenate the culture for growing the cells or microorganisms.
2. The method as recited in claim 1 , wherein the step of blowing the stream of gas comprises blowing the stream of gas so that the gas directly adjacent to the top surface of the culture has a velocity of at least 25 m/sec.
3. The method as recited in claim 1 , wherein the step of blowing the stream of gas comprises blowing the stream of gas into the compartment of the container at a flow rate of at least 0.08 VVM.
4. The method as recited in claim 1 , wherein the container comprises a flexible bag having a bottom wall, a top wall and an encircling sidewall extending therebetween, the step of blowing the stream of gas comprising delivering the gas through a first opening formed on the sidewall of the container, wherein the opening is above the to of the medium.
5. The method as recited in claim 4 , wherein the step of delivering comprises delivering the gas through a nozzle coupled with the first opening.
6. The method as recited in claim 1 , wherein the gas stream produces a kLa factor in the culture of at least 3.
7. The method as recited in claim 1 , wherein the step of blowing the stream of gas comprises:
advancing a tube through a first opening formed on the container so that a tip of the tube is located within the compartment; and
blowing the stream of gas out of the tube so that the stream of gas passes over the at least a portion of the top surface of the culture.
8. The method as recited in claim 7 , further comprising advancing the tube through the first opening so that the tip of the tube is within about 1 cm to about 10 cm from the top surface of the culture when blowing the stream of gas out of the tube.
9. The method as recited in claim 1 , wherein the step of blowing the stream of gas over the at least a portion of top surface of the culture occurs without sparging gas bubbles into the culture.
10. The method as recited in claim 1 , wherein the top surface of the culture is at a first elevation within the container during the step of delivering the gas, the step of blowing the stream of gas over the at least a portion of the top surface of the culture occurring without sparging gas bubbles into the culture while the culture is at the first elevation, and the method further comprising:
a) adding medium to the culture within the container so as to raise the top surface of the culture to a second elevation within the compartment; and
b) sparging gas bubbles containing oxygen into the culture after the top surface has been raised to the second elevation within the compartment.
11. The method as recited in claim 1 , wherein the step of blowing the stream of gas comprises blowing the stream of gas horizontally or substantially horizontally over the at least a portion of the top surface.
12. The method as recited in claim 1 , wherein the stream of gas is blown over the at least a portion of the top surface at a downward incline.
13. The method as recited in claim 1 , wherein a nozzle is positioned within the compartment of the container, the nozzle having an encircling sidewall with a plurality of radially spaced apart outlets extending around the sidewall, the step of blowing the stream of the gas comprising blowing the gas through the plurality of outlets on the nozzle.
14. The method as recited in claim 13 , further comprising raising the nozzle within the compartment of the container as the volume of culture increases within the compartment.
15. The method as recited in claim 1 , wherein a tube having a plurality of lumens is disposed within the compartment of the container, a plurality of nozzles being coupled with the tube at spaced apart locations and having at least one outlet thereon, each of the plurality of nozzles being coupled with a corresponding one of the plurality of lumens, the step of blowing the stream of the gas comprising consecutively blowing the gas through the outlet of each of the plurality of nozzles as the volume of the culture within the compartment increases.
16. The method as recited in claim 1 , wherein the step of mixing the culture comprises rotating a mixing element within the container.
17. The method as recited in claim 1 , wherein the step of mixing is performed independently of blowing the stream of gas.