External-loop perfusion air-lift bioreactor

• US 5,342,781 A
• Filed: 07/15/1993
• Issued: 08/30/1994
• Est. Priority Date: 07/15/1993
• Status: Expired due to Term

• Current Assignee: University of Hawai'i
• Original Assignee: University of Hawai'i
• Inventors: Su, Wei-Wen W.
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): Ludlow, Jan M.
• Application Number:
  US08/092,235
• Time in Patent Office: 411 Days
• Field of Search: 435/286, 435/287, 435/299, 435/313, 435/314, 435/813, 435/311, 261/77, 261/123, 210/194, 210/220, 210/221.2
• US Class Current: 435/296.1
• CPC Class Codes: C12M 27/20 Baffles; Ribs; Ribbons; Auger vanes
• CPC Class Codes: C12M 29/08 Air lift
• CPC Class Codes: C12M 29/10 Perfusion
• CPC Class Codes: C12M 29/18 External loop; Means for reintroduction of fermented biomass or liquid percolate loop type reactors for chemical or physical processes B01J19/2435
• CPC Class Codes: Y10S 435/813 Continuous fermentation

Abstract

An external-loop perfusion bioreactor for cultivating microbial, plant, animal or insect cells to produce valuable metabolites has a riser conduit; a cell culture medium inlet in the riser conduit; an inlet for an oxygen containing gas in the riser conduit; a downcomer conduit, having an upper portion and a lower portion, the upper portion of the downcomer conduit being in the shape of a truncated cone; an upper and lower transfer conduit connecting the riser conduit and the downcomer conduit; a spent medium outlet port defining a liquid level surface in the upper portion of the downcomer conduit; and a baffle means having a fluid impermeable wall for creating a settling zone in the upper portion of the downcomer conduit. A series of conical lamellar settling surfaces can be arranged in the settling zone to enhance particle separation from the aqueous medium.

Claims

1. An external-loop perfusion bioreactor for cell culture comprising:

(a) a riser conduit;

(b) cell culture medium inlet in said riser conduit;

(c) an inlet for an oxygen-containing gas in said riser conduit;

(d) a downcomer conduit, having an upper portion and a lower portion, said upper portion of said downcomer conduit being in the shape of a truncated cone;

(e) an upper transfer conduit connecting an upper portion of said riser conduit to said upper portion of said downcomer conduit;

(f) a lower transfer conduit connecting said lower portion of said downcomer conduit to a lower portion of said riser conduit;

(g) a spent medium outlet port defining a liquid level surface in said upper portion of said downcomer conduit; and

(h) baffle means comprising a fluid impermeable wall defining a settling zone in said upper portion of said downcomer conduit, wherein said fluid impermeable wall comprises a generally T-shaped baffle conduit having a baffle conduit inlet connected to said upper transfer conduit and two baffle conduit outlets, a first one of said baffle outlets extending through said upper portion of said downcomer conduit and above said liquid level surface, and a second one of said baffle outlets extending downward from said liquid surface.

2. A bioreactor as in claim 1 wherein a lower portion of said truncated cone terminates at a position along a length of said downcomer conduit and said second baffle outlet terminates at a position above the position at which said truncated cone terminates.

3. A bioreactor as in claim 1 further comprising a fluid surface aerator positioned in said downcomer conduit for aerating liquid at said liquid level surface.

4. A bioreactor as in claim 1 further comprising oxygen permeable membrane tubing positioned within said settling zone.

5. A bioreactor as in claim 1, further comprising at least one settling surface in the shape of a truncated cone positioned in said settling zone.

6. A bioreactor as in claim 5 including a series of lamellar settling surfaces, each said surface being in the shape of a truncated cone, arranged in said settling zone.

7. A bioreactor for cell culture comprising:

(a) a riser conduit having a generally cylindrical shape, an upper portion and a lower portion, a cell culture medium inlet, and an oxygen-containing gas inlet in said lower portion, a centerline of said riser conduit between said lower and upper portions of said riser conduit defining a substantially vertical axis;

(b) a downcomer conduit having an upper portion and a lower portion, a centerline of said downcomer conduit between said upper and lower portions defining a substantially vertical axis, said upper portion of said downcomer conduit having the shape of a truncated cone, and said upper portion of said downcomer conduit including a spent medium outlet, said spent medium outlet defining a liquid level surface;

(c) an upper transfer conduit connecting said upper portion of said riser conduit and said upper portion of said downcomer conduit, a centerline of said upper transfer conduit defining a substantially horizontal fluid flow path therebetween;

(d) a lower transfer conduit connecting said lower portion of said downcomer conduit and said lower portion of said riser conduit, and a centerline of said lower transfer conduit defining a substantially horizontal fluid flow path therebetween;

wherein said upper transfer conduit extends into said upper portion of said downcomer and has two outlet conduits, a first one of said outlet conduits extending in a direction generally parallel to said vertical axis, and forming an outlet port above said liquid level surface, a second one of said outlet conduits extending in a direction generally parallel to said vertical axis and in a direction opposite said direction in which said first outlet conduit extends, and said second outlet conduit forming an outlet port in a lower portion of said truncated cone.