Bioreactor using acoustic standing waves

Patent metadata

Field	Value
Publication number	US-9752114-B2
Application number	US-201715453582-A
Country	US
Kind code	B2
Filing date	Mar 8, 2017
Priority date	Mar 15, 2012
Publication date	Sep 5, 2017
Grant date	Sep 5, 2017

Abstract

A perfusion bioreactor includes at least one ultrasonic transducer that can acoustically generate a multi-dimensional standing wave. The standing wave can be used to retain cells in the bioreactor, and can also be utilized to dewater or further harvest product from the waste materials produced in a bioreactor.

First claim

The invention claimed is:

1. A system comprising:
a bioreactor;
a primary clarification stage, the primary clarification stage including an acoustophoretic separator downstream of and fluidly connected to the bioreactor, the acoustophoretic separator comprising:
a flow chamber; and
an ultrasonic transducer and a reflector located opposite the ultrasonic transducer and configured to produce a multi-dimensional standing wave in the flow chamber when the ultrasonic transducer is actuated; and

a secondary clarification stage downstream of the primary clarification stage.

2. The system of claim 1 , wherein the secondary clarification stage includes a filtration device fluidly connected to the acoustophoretic separator.

3. The system of claim 2 , wherein the filtration device is one or more of a depth filter, a sterile filter, a tangential flow filter, or a crossflow filter.

4. The system of claim 1 , wherein the secondary clarification stage is configured to isolate a desired product by size exclusion filtration.

5. The system of claim 1 , wherein the secondary clarification stage includes a plurality of filtration devices arranged in series.

6. The system of claim 5 wherein at least one of the plurality of filtration devices is a separation column and another of the plurality of filtration devices is a porous filter, the porous filter being located upstream of the separation column and fluidly connected thereto.

7. The system of claim 1 , wherein the multi-dimensional standing wave includes an axial force component and a lateral force component which are of the same order of magnitude.

8. The system of claim 1 , wherein the secondary clarification stage is adapted to trap at least some material that passes through the primary clarification stage.

9. The system of claim 1 , wherein the secondary clarification stage includes a second acoustophoretic separator comprising a second ultrasonic transducer and opposed reflector configured to produce a second multi-dimensional standing wave in the second acoustophoretic separator when the second ultrasonic transducer is actuated, the second multi-dimensional standing wave being adapted to trap at least some material that passes through the primary clarification stage.

10. The system of claim 1 , wherein the bioreactor is a perfusion bioreactor.

11. A process of isolating and recovering desired product from a cell culture media, comprising:
receiving the cell culture media at a primary clarification stage, the primary clarification stage including an acoustophoretic separator downstream of and fluidly connected to the bioreactor, wherein the acoustophoretic separator comprises:
a flow chamber; and
an ultrasonic transducer and a reflector located opposite the ultrasonic transducer;

providing an output of the acoustophoretic separator to a secondary clarification stage downstream of the primary filtration stage; and
recovering the desired product from the secondary clarification stage.

12. The process of claim 11 , further comprising sending the cell culture media from the flow chamber back to the bioreactor through a recycle outlet of the acoustophoretic separator.

13. The process of claim 11 , wherein the secondary clarification stage includes a filtration device fluidly connected to the acoustophoretic separator.

14. The process of claim 13 , wherein the filtration device is one or more of a depth filter, a sterile filter or a crossflow filter.

15. The process of claim 11 , further comprising isolating the desired product by size exclusion filtration.

16. The process of claim 11 , further comprising arranging the secondary clarification stage as a plurality of filtration devices arranged in series.

17. The process of claim 16 , wherein at least one of the plurality of filtration devices is a separation column and another of the plurality of filtration devices is a porous filter, the porous filter being located upstream of the separation column and fluidly connected thereto.

18. The process of claim 11 , further comprising actuating the ultrasonic transducer to generate a multi-dimensional standing wave with an axial force component and a lateral force component which are of the same order of magnitude.

19. The process of claim 11 , further comprising trapping at least some material with the secondary clarification stage that passes through the primary clarification stage.

20. The process of claim 11 , further comprising actuating an ultrasonic transducer in a second acoustophoretic separator in the secondary clarification stage to produce a multi-dimensional standing wave in the second acoustophoretic separator, the multi-dimensional standing wave being adapted to trap at least some material that passes through the primary clarification stage.

Assignees

• Flodesign Sonics Inc
• Flodesign Sonics Inc

Inventors

• Lipkens Bart
• Masi Louis
• Kowalski Iii Stanley
• Presz Jr Walter M
• Dionne Jason
• Dutra Brian
• Mercado Ari
• Kennedy Iii Thomas J
• Martin Arthur
• Rozembersky John

Classifications

• C12M47/10 Primary

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

• C12M29/18

  External loop; Means for reintroduction of fermented biomass or liquid percolate (loop type reactors for chemical or physical processes B01J19/2435) · CPC title

• C12M47/02

  Separating microorganisms from the culture medium; Concentration of biomass (separating microorganisms from their culture media C12N1/02) · CPC title

• C12M29/10

  Perfusion · CPC title

• B01D21/283

  Settling tanks provided with vibrators · CPC title