Bioreactor using acoustic standing waves

Patent metadata

Field	Value
Publication number	US-9783775-B2
Application number	US-201715432737-A
Country	US
Kind code	B2
Filing date	Feb 14, 2017
Priority date	Mar 15, 2012
Publication date	Oct 10, 2017
Grant date	Oct 10, 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;
an acoustophoretic separator downstream of and fluidly connected to the bioreactor, comprising:
a flow chamber; and
an ultrasonic transducer and a reflector located opposite the ultrasonic transducer so as to produce a multi-dimensional standing wave in the flow chamber; and

a downstream filtration stage downstream of and fluidly connected to the acoustophoretic separator.

2. The system of claim 1 , wherein the downstream filtration stage is selected from the group consisting of depth filters, sterile filters, and crossflow filters.

3. The system of claim 1 , wherein the downstream filtration stage isolates the desired product by size exclusion filtration.

4. The system of claim 1 , wherein the downstream filtration stage includes a plurality of filtration stages arranged in series.

5. The system of claim 4 , wherein at least one of the plurality of filtration stages is a separation column and another of the plurality of filtration stages is a porous filter, the porous filter located upstream of the separation column and fluidly connected thereto.

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

7. The system of claim 1 , wherein the downstream filtration stage is a second acoustophoretic separator comprising an ultrasonic transducer-reflector pair driven to produce a multi-dimensional standing wave in the second acoustophoretic separator that is adapted to trap desired product that is not trapped in the first acoustophoretic separator.

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

9. A process of isolating and recovering a desired product from a cell culture media, comprising:
sending the cell culture media from a bioreactor to an acoustophoretic separator, wherein the acoustophoretic separator comprises:
a flow chamber; and
an ultrasonic transducer and a reflector located opposite the ultrasonic transducer;

producing a multi-dimensional standing wave in the flow chamber to separate the desired product from the cell culture media;
passing a concentrated flow of the desired product from the acoustophoretic separator to a downstream filtration stage;
recovering the desired product from the downstream filtration stage.

10. The process of claim 9 , further comprising sending the cell culture media from the flow chamber back to the bioreactor through a recycle outlet of the acoustophoretic separator.

11. A system comprising:
a bioreactor;
an upstream filtration stage fluidly connected to the bioreactor and upstream of an acoustophoretic separator; and
the acoustophoretic separator fluidly connected to and downstream of the upstream filtration stage, the acoustophoretic separator comprising:
a flow chamber; and
an ultrasonic transducer and a reflector located opposite the ultrasonic transducer so as to produce a multi-dimensional standing wave in the flow chamber;
a recycle outlet downstream of the flow chamber connected to a recycle inlet of the reaction vessel, for sending the associated fluid containing cells back to the bioreactor.

12. The system of claim 11 , wherein the upstream filtration stage is selected from the group consisting of depth filters, sterile filters, and crossflow filters.

13. The system of claim 11 , wherein the upstream filtration stage isolates the desired product by size exclusion filtration.

14. The system of claim 11 , wherein the upstream filtration stage includes a plurality of filtration stages arranged in series.

15. The system of claim 14 , wherein at least one of the plurality of filtration stages is a separation column and another of the plurality of filtration stages is a porous filter, the porous filter located upstream of the separation column and fluidly connected thereto.

16. The system of claim 11 , wherein the multi-dimensional standing wave has an axial force component and a lateral force component which are of the same order of magnitude.

17. The system of claim 11 , wherein the upstream filtration stage is a second acoustophoretic separator comprising an ultrasonic transducer-reflector pair driven to produce a second multi-dimensional standing wave in the second acoustophoretic separator.

18. The system of claim 11 , wherein the bioreactor is a perfusion bioreactor.

19. The system of claim 17 , wherein the second multi-dimensional standing wave has an axial force component and a lateral force component which are of the same order of magnitude.

Assignees

• 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

Classifications

• C12M29/10

  Perfusion · 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

• C12M33/14

  with filters, sieves or membranes · CPC title

• C12M47/02 Primary

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