Bioreactor using acoustic standing waves

Patent metadata

Field	Value
Publication number	US-9738867-B2
Application number	US-201715432888-A
Country	US
Kind code	B2
Filing date	Feb 14, 2017
Priority date	Mar 15, 2012
Publication date	Aug 22, 2017
Grant date	Aug 22, 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 method for obtaining expanded cells, comprising:
culturing cells in a fluid medium in a bioreactor to expand the cells;
sending a portion of the fluid medium containing the expanded cells from the bioreactor to an acoustophoretic separator that comprises:
a flow chamber through which the portion of the fluid medium flows; and
an ultrasonic transducer and a reflector located opposite the ultrasonic transducer so as to produce a multi-dimensional acoustic standing wave in the flow chamber;

driving the transducer to produce the multi-dimensional acoustic standing wave and create a concentrated flow of the expanded cells; and
further processing the concentrated flow of the expanded cells.

2. The method of claim 1 , wherein the further processing is adapted to isolate or recover the expanded cells from the concentrated flow.

3. The method of claim 1 , wherein the further processing is selected from the group consisting of cell washing, cell concentration, and cell fractionation.

4. The method 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.

5. A method for obtaining biomolecules, comprising:
culturing cells in a fluid medium in a bioreactor, wherein the cells produce the biomolecules;
sending a portion of the fluid medium containing the biomolecules from the bioreactor to an acoustophoretic separator that comprises:
a flow chamber through which the portion of the fluid medium flows; and
an ultrasonic transducer and a reflector located opposite the ultrasonic transducer so as to produce a multi-dimensional acoustic standing wave in the flow chamber;

driving the transducer to produce the multi-dimensional acoustic standing wave and create a concentrated flow of the biomolecules; and
further processing the concentrated flow of the biomolecules.

6. The method of claim 5 , wherein the further processing is adapted to isolate or recover the biomolecules from the concentrated flow.

7. The method of claim 5 , 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.

8. The method of claim 5 , wherein the biomolecules are selected from the group consisting of recombinant proteins and monoclonal antibodies.

9. A method for obtaining viruses or exosomes, comprising:
culturing cells in a fluid medium in a bioreactor, wherein the cells are engineered to produce the viruses or exosomes;
sending a portion of the fluid medium containing the viruses or exosomes from the bioreactor to an acoustophoretic separator that comprises:
a flow chamber through which the portion of the fluid medium flows; and
an ultrasonic transducer and a reflector located opposite the ultrasonic transducer so as to produce a multi-dimensional acoustic standing wave in the flow chamber;

driving the transducer to produce the multi-dimensional acoustic standing wave and create a concentrated flow of the viruses or exosomes; and
further processing the concentrated flow of the viruses or exosomes.

10. The method of claim 9 , wherein the further processing is adapted to isolate or recover the viruses or exosomes from the concentrated flow.

11. The method of claim 9 , 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.

12. A method for obtaining a desired product, comprising:
sending a fluid medium containing the desired product from a bioreactor to an acoustophoretic separator that comprises:
a flow chamber through which the fluid medium flows; and
an ultrasonic transducer and a reflector located opposite the ultrasonic transducer so as to produce a multi-dimensional acoustic standing wave in the flow chamber;

driving the transducer to produce the multi-dimensional acoustic standing wave and create a concentrated flow of the desired product; and
further processing the concentrated flow of the desired product to isolate or recover the desired product.

13. The method of claim 12 , wherein the desired product is expanded cells, biomolecules, viruses, or exosomes.

14. A system for obtaining a desired product, comprising:
a bioreactor;
an acoustophoretic separator fluidly connected to and downstream of the bioreactor, the acoustophoretic separator comprising:
a flow chamber for receiving a fluid medium containing the desired product from the bioreactor;
an ultrasonic transducer and a reflector located opposite the ultrasonic transducer so as to produce a multi-dimensional acoustic standing wave in the flow chamber that separates the fluid medium and the desired product; and
a product outlet for recovering a concentrated flow of the desired product; and

at least one device for further processing of the concentrated flow, the at least one device located downstream of the acoustophoretic separator.

15. The system of claim 14 , wherein the at least one device for further processing is adapted to isolate or recover the desired product from the concentrated flow of the desired product.

16. The system of claim 14 , wherein the at least one device for further processing performs a process selected from the group consisting of cell washing, cell concentration, and cell fractionation.

17. The system of claim 14 , wherein the desired product is expanded cells, biomolecules, viruses, or exosomes.

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

• C12M47/02

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

• C12M35/04

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

• C12P21/02

  having a known sequence of two or more amino acids, e.g. glutathione · CPC title

• C12M47/10 Primary

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

• C12M47/04

  Cell isolation or sorting (purging biological preparations of unwanted cells C12N5/0081, determining the presence or kind of microorganism C12Q1/04) · CPC title