Acoustic bioreactor processes

Patent metadata

Field	Value
Publication number	US-9422328-B2
Application number	US-201414329723-A
Country	US
Kind code	B2
Filing date	Jul 11, 2014
Priority date	Mar 15, 2012
Publication date	Aug 23, 2016
Grant date	Aug 23, 2016

Abstract

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.

First claim

The invention claimed is:

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.

Assignees

• Flodesign Sonics Inc

Inventors

• Kennedy Iii Thomas J
• Lipkens Bart
• Masi Louis
• Kowalski Iii Stanley
• Leidel Chris

Classifications

• B01D17/06

  Separation of liquids from each other by electricity · CPC title

• B01D43/00

  Separating particles from liquids, or liquids from solids, otherwise than by sedimentation or filtration (flotation processes B03D1/00; drying solid materials or objects F26B) · CPC title

• C12M47/10

  Separation or concentration of fermentation products (bioreactors combined with means for distillation or extraction of liquid fuel C12M43/02) · CPC title

• C12M35/02

  Electrical or electromagnetic means, e.g. for electroporation or for cell fusion · CPC title

• C12M35/04

  Mechanical means, e.g. sonic waves, stretching forces, pressure or shear stimuli · CPC title