Acoustic bioreactor processes
A series of multi-dimensional acoustic standing waves is set up inside a growth volume of a bioreactor. The acoustic standing waves are used to hold a cell culture in place as a nutrient fluid stream flows through the cell culture. Biomolecules produced by the cell culture are collected by the nutrient fluid stream and separated downstream of the cell culture.
1. A process for collecting biomolecules from a cell culture, comprising:
suspending the cell culture in a growth volume of a bioreactor, the bioreactor including at least one ultrasonic transducer and a reflector located opposite the at least one ultrasonic transducer, each ultrasonic transducer being driven to produce a multi-dimensional acoustic standing wave that holds the cell culture in the growth volume; and
flowing a nutrient fluid stream through the cell culture to collect the biomolecules.
2. The process of claim 1 , wherein the bioreactor further comprises a secondary filtering system located between the growth volume and a bioreactor outlet.
3. The process of claim 2 , further comprising activating the secondary filtering system if the multi-dimensional acoustic standing wave fails.
4. The process of claim 1 , wherein the multi-dimensional acoustic standing wave is in resonance.
5. The process of claim 1 , wherein the at least one ultrasonic transducer is an array of elements.
6. The process of claim 1 , wherein each ultrasonic transducer produces a plurality of multi-dimensional acoustic standing waves.
7. The process of claim 1 , wherein the bioreactor does not include an impeller within the growth volume.
8. The process of claim 1 , wherein the cell culture is composed of Chinese hamster ovary (CHO) cells.
9. The process of claim 1 , wherein the biomolecules are monoclonal antibodies or recombinant proteins.
10. The process of claim 1 , wherein the multi-dimensional acoustic standing wave has an axial force component and a lateral force component which are of the same order of magnitude.
11. The process of claim 1 , wherein the ultrasonic transducer comprises a piezoelectric material that can vibrate in a higher order mode shape.
12. The process of claim 11 , wherein the piezoelectric material has a rectangular shape.
13. The process of claim 1 , wherein the ultrasonic transducer comprises:
a housing having a top end, a bottom end, and an interior volume; and
a crystal at the bottom end of the housing having an exposed exterior surface and an interior surface, the crystal being able to vibrate when driven by a voltage signal.
14. The process of claim 13 , wherein a backing layer contacts the interior surface of the crystal, the backing layer being made of a substantially acoustically transparent material.
15. The process of claim 14 , wherein the substantially acoustically transparent material is balsa wood, cork, or foam.
16. The process of claim 14 , wherein the substantially acoustically transparent material has a thickness of up to 1 inch.
17. The process of claim 14 , wherein the substantially acoustically transparent material is in the form of a lattice.
18. The process of claim 13 , wherein an exterior surface of the crystal is covered by a wear surface material with a thickness of a half wavelength or less, the wear surface material being a urethane, epoxy, or silicone coating, or being made of aluminum oxide.
19. The process of claim 13 , wherein the crystal has no backing layer or wear layer.
20. The process of claim 1 , wherein the multi-dimensional acoustic standing wave is a three-dimensional standing wave.