Continuous perfusion bioreactor system

Patent metadata

Field	Value
Publication number	US-11834643-B2
Application number	US-202117394864-A
Country	US
Kind code	B2
Filing date	Aug 5, 2021
Priority date	Jul 30, 2007
Publication date	Dec 5, 2023
Grant date	Dec 5, 2023

Abstract

Systems and methods for containing and manipulating liquids, including vessels and unit operations or components of cell culture, cell containment, bioreactor, and/or pharmaceutical manufacturing systems. In certain embodiments, such vessels and unit operations are directed to continuous perfusion reactor or bioreactor systems and may include one or more disposable components. In one aspect, a system includes an apparatus in the form of a bioreactor for harvesting cells. The apparatus may include a disposable, collapsible bag for containing a liquid, the collapsible bag in fluid communication with a liquid-solids separation device. An outlet of the collapsible bag may be connected to an inlet of the separation device, and an outlet of the separation device may be connected to an inlet of the collapsible bag. After separating the cells from the liquid in the separation device, the cells can flow back into the collapsible bag for re-harvesting.

First claim

What is claimed:

1. A bioreactor apparatus, comprising:
a first reusable support structure with walls configured to support a first collapsible bag containing a solids-bearing liquid, the first collapsible bag containing at least a first inlet and a first outlet;
a second reusable support structure with walls configured to support a second collapsible bag fluidically coupled via a first fluid connection from the first outlet of the first collapsible bag to a first inlet of the second collapsible bag;
wherein the first fluid connection is accomplished through the walls of the first and second reusable support structures; and
wherein the second collapsible bag is configured to separate solids from the solids-bearing liquid received from the first collapsible bag and return a solids-separated liquid to the first collapsible bag via the first inlet of the first collapsible bag.

2. The bioreactor apparatus of claim 1 , further comprising:
wherein the solids-bearing liquid in the first collapsible bag at a first concentration of a component is introduced via the first fluid connection to the second collapsible bag;
the second collapsible bag configured to alter the concentration of the component in the solids-bearing liquid to a second concentration; and
wherein the solids-bearing liquid at a second concentration of the component is returned to the first collapsible bag.

3. The bioreactor apparatus of claim 2 , further comprising:
wherein the solids-bearing liquid at second concentrations of at least one or more additional components is returned to the first collapsible bag.

4. The bioreactor apparatus of claim 1 , further comprising:
wherein the first collapsible bag is in continuous fluid communication with the second collapsible bag during operation.

5. The bioreactor apparatus of claim 1 , further comprising:
wherein the first collapsible bag is in periodic fluid communication with the second collapsible bag during operation.

6. The bioreactor apparatus of claim 1 , further comprising:
wherein the solids are at least one selected from the group of: solid objects, viable organisms, non-viable organisms, precipitate, a cell, and a cell attached to a particle.

7. The bioreactor apparatus of claim 3 , further comprising:
wherein the particle to which a cell is attached is at least one selected from the group of: a solid sphere, a fiber, and a gelatinous particle.

8. The bioreactor apparatus of claim 1 , further comprising:
wherein a solids-separating device is positioned on a surface of or in an internal portion of either the first or second collapsible bags.

9. The bioreactor apparatus of claim 8 , further comprising:
wherein the solids-separating device is at least one selected from the group of: a spin filter, a centrifuge, a settling device, a microporous frit, an ultrafiltration membrane, a hollow fiber filter, a settling device, and a plate and frame filtration device.

10. The bioreactor apparatus of claim 1 , further comprising:
wherein the second collapsible bag forms at least one selected from the group of: a media storage tank, a buffer storage tank, a mixing system, and a batch harvesting tank.

11. The bioreactor apparatus of claim 1 , further comprising:
at least one or more sensors connected to at least one or more process controllers configured to control at least one environmental parameter in either the first or second disposable bags in response to outputs from the at least one or more sensors.

12. A method for operating a bioreactor, comprising:
providing a first collapsible bag containing a solids-bearing liquid, the first collapsible bag further configured with at least a first inlet and a first outlet;
providing a first reusable support structure with walls configured to support the first collapsible bag;
providing a second collapsible bag with at least one inlet and one outlet;
providing a second reusable support structure configured to support the first collapsible bag;
fluidically coupling the first outlet of the first collapsible bag to an inlet of the second collapsible bag through the walls of the first and second reusable support structures;
transferring the solids-bearing liquid from the first collapsible bag to the second collapsible bag via the fluidic coupling;
separating solids from the solids-bearing liquid in the second collapsible bag; and
returning a solids-separated liquid from the second collapsible bag to the first collapsible bag via the first inlet of the first collapsible bag.

13. The method of operating a bioreactor of claim 12 , further comprising:
introducing the solids-bearing liquid in the first collapsible bag at a first concentration of a component via the first fluid connection to the second collapsible bag;
altering via the second collapsible bag the concentration of the component in the solids-bearing liquid to a second concentration; and
returning the solids-bearing liquid at a second concentration to the first collapsible bag.

14. The method of operating a bioreactor of claim 12 , further comprising:
returning the solids-bearing liquid at a second concentration of at least one or more additional components to the first collapsible bag.

15. The method of operating a bioreactor of claim 12 , further comprising:
maintaining the first collapsible bag in continuous fluid communication with the second collapsible bag during operation.

16. The method of operating a bioreactor of claim 12 , further comprising:
the first collapsible bag in periodic fluid communication with the second collapsible bag during operation.

17. The method of operating a bioreactor of claim 12 , further comprising:
providing a solids-separating device positioned on the surface of or in an internal portion of either the first or second collapsible bags.

18. The method of operating a bioreactor of claim 17 , further comprising:
wherein the provided solids-separating device is at least one selected from the group of: a spin filter, a centrifuge, a settling device, a microporous frit, an ultrafiltration membrane, a hollow fiber filter, a settling device, and a plate and frame filtration device.

19. The method of operating a bioreactor of claim 12 , further comprising:
further configuring the second apparatus to perform the function of at least one selected from the group of: a media storage tank, a buffer storage tank, a mixing system, and a batch harvesting tank.

20. The method of operating a bioreactor of claim 12 , further comprising:
connecting at least one sensor to at least one process controller configured to control at least one environmental parameter in either the first or second disposable bags in response to the sensor reading.

21. A bioreactor apparatus, comprising:
a first reusable support structure with walls configured to support a first collapsible bag containing a solids-bearing liquid, the first collapsible bag containing at least a first inlet and a first outlet;
a second reusable support structure with walls configured to support a second collapsible bag fluidically coupled via a first fluid connection from the first outlet of the first collapsible bag to a first inlet of the second collapsible bag;
wherein the first fluid connection is accomplished through openings in the walls of the first and second reusable support structures;
wherein the first fluid connection is configured to permit movement of the first and second apparatuses relative to each other; and
wherein the second collapsible bag is

Assignees

• Global Life Sciences Solutions Usa Llc
• Global Life Sciences Usa Llc

Inventors

• Galliher Parrish M
• Hodge Geoffrey L
• Fisher Michael
• Guertin Patrick
• Mardirosian Dan

Classifications

• C12M29/10 Primary

  Perfusion · CPC title

• B01D29/13

  Supported filter elements · CPC title

• C12M23/14

  Bags · CPC title

• C12M23/26

  flexible (flexible containers for laboratory use B01L3/505) · CPC title

• C12M23/48

  Holding appliances; Racks; Supports (holding devices for laboratory apparatus B01L9/00) · CPC title