Centrifugal fermentation process

• US 6,133,019 A
• Filed: 07/13/1998
• Issued: 10/17/2000
• Est. Priority Date: 03/28/1995
• Status: Expired due to Term

• Current Assignee: Sartorius Stedim North America Inc. (Sartorius AG)
• Original Assignee: Kinetic Systems Incorporated (Kinetics Holding GmbH)
• Inventors: Herman, Heath H.
• Primary Examiner(s): Redding, David A.
• Application Number:
  US09/115,109
• Time in Patent Office: 827 Days
• Field of Search: 435/285.1, 435/286.1, 435/286.5, 435/286.7, 435/289.1, 435/813, 935/85, 935/87, 935/88
• US Class Current: 435/286.1
• CPC Class Codes: C12M 27/10 Rotating vessel
• CPC Class Codes: C12M 41/00 Means for regulation, monitoring, measurement or control, e.g. flow regulation controlling or regulating chemical, physical or physicochemical processes B01J19/0006; heating or cooling apparatus for laboratory use B01L7/00; electro optical investigation of individual particles, flow cytometers G01N15/14; automatic analysis G01N35/00; controlling or regulating in general G06N
• CPC Class Codes: Y10S 435/813 Continuous fermentation

Abstract

The present invention comprises a novel culture method and device in which living cells or subcellular biocatalysts are immobilized by the opposition of a centrifugal force field and a liquid flow field. The immobilized cells or biocatalysts are ordered into a three-dimensional array of articles, the density of which is determined by the particle size, shape, intrinsic density and by the selection of combinations of parameters such as liquid flow rate and angular velocity of rotation.

Claims

1. An apparatus for containing a biocatalyst at a desired location within a liquid flow path, said apparatus for use within a gravitational field and comprising:

A) a rotable assembly defining

1) a shaft;

2) a rotor body, attached to said shaft, defining one or more bioreactor chambers disposed within said rotor body and spaced radially apart from said shaft, each of said bioreactor chambers including a liquid inlet port and a liquid outlet port and configured to allow for the flow of liquid from said inlet port to said outlet port;

3) one or more liquid input lines dimensioned for liquid communication with said one or more bioreactor chambers; and

4) one or more liquid output lines dimensioned for liquid communication with said one or more bioreactor chambers;

B) means for providing a flow of liquid not including a gaseous phase and at hydraulic pressures greater than atmospheric from one or more inlet ports of one or more of said chambers, through said one or more of said chambers and out of one or more outlet ports of said one or more of said chambers, such that a liquid flow force is imparted upon said biocatalyst inside one or more of said chambers by said liquid flow;

C) means for supporting said rotor body for rotation about a rotational axis substantially fixed relative to said gravitational field; and

D) means for rotating said rotor body about said rotational axis to create a centrifugal field acting upon one or more of said chambers tending to oppose said liquid flow force;

such that during the rotation of said rotor body about said rotational axis and during the flow of said liquid, the gravitational force contributes to the resultant vector summation of all forces acting on said biocatalyst, and said gravitational, liquid, and centrifugal forces substantially immobilize said biocatalyst at a position in said rotor body.

2. The apparatus as claimed in claim 1, wherein said chamber includes a major axis, and wherein said major axis is substantially parallel to said centrifugal force field.

3. The apparatus as claimed in claim 1, wherein said chamber includes a major axis, and wherein said major axis is at an angle between approximately 0 and 90 degrees to the centrifugal force field.

4. The apparatus as claimed in claim 1, wherein said chamber defines an interior major portion which tapers outwardly in a downstream flow direction.

5. The apparatus as claimed in claim 1, wherein said one or more liquid input lines passes through an axial portion of said shaft.

6. The apparatus as claimed in claim 1, wherein said one or more liquid output lines passes through an axial portion of said shaft.

7. The apparatus as claimed in claim 1, wherein a volume defined by one or more of said bioreactor chambers includes a truncated cone portion, a cylindrical portion, and a conical portion.

8. The apparatus as claimed in claim 7, wherein said truncated cone portion is disposed between said conical portion and said cylindrical portion.

9. The apparatus as claimed in claim 8, further including a machined conical recess that communicates with said cylindrical portion.

10. An apparatus for containing a biocatalyst at a desired location within a liquid flow path, said apparatus for use within a gravitational field and comprising:

A) a rotable assembly defining

1) a shaft having an axial liquid input channel;

2) a rotor body mounted to said shaft so that rotation of said shaft causes said rotor body to rotate about a longitudinal axis of said shaft;

3) one or more bioreactor chambers disposed within said rotor body and spaced radially apart from said shaft, each of said chambers including a liquid inlet port and a liquid outlet port and being configured to allow for the flow of liquid from said inlet port to said outlet port;

4) one or more input liquid transport lines dimensioned for liquid communication between said axial liquid input channel and said one or more bioreactor chambers; and

5) one or more output liquid transport lines dimensioned for liquid communication between said one or more bioreactor chambers and an axial liquid output channel disposed within said shaft;

said rotable assembly being dimensioned so that liquid may flow into said axial liquid input channel, through said one or more input liquid transport lines, through said one or more bioreactor chambers, through said output liquid transport lines, and out said axial liquid output channel;

B) means for providing a flow of liquid not including a gaseous phase and at hydraulic pressures greater than atmospheric from one or more inlet ports of one or more of said chambers, through said one or more of said chambers and out of one or more outlet ports of said one or more of said chambers, such that a liquid flow force is imparted upon said biocatalyst inside one or more of said chambers by said liquid flow;

C) means for supporting said rotor body for rotation about a rotational axis substantially fixed relative to said gravitational field; and

D) means for rotating said rotor body about said rotational axis to create a centrifugal field acting upon one or more of said chambers tending to oppose said liquid flow force;

such that during the rotation of said rotor body about said rotational axis and during the flow of said liquid, the gravitational force contributes to the resultant vector summation of all forces acting on said biocatalyst, and said gravitational, liquid, and centrifugal forces substantially immobilize said biocatalyst at a position in said rotor body.

11. The apparatus as claimed in claim 10, wherein one or more of said one or more bioreactor chambers has a chamber input port for receiving liquid from an input liquid transport line and a chamber output port for transferring liquid into an output liquid transport line, and wherein a radial distance between an axis of rotation of said shaft and said chamber input port is greater than a radial distance between an axis of rotation of said shaft and said chamber output port.

12. The apparatus as claimed in claim 10, wherein said device includes three bioreactor chambers.

13. The apparatus as claimed in claim 12, wherein said three bioreactor chambers are spaced apart from one another so that a center axis of each of said three bioreactor chambers is angularly spaced apart from a center axis of each of the other two bioreactor chambers by approximately 120 degrees.

14. The apparatus as claimed in claim 12, wherein one or more of said bioreactor chambers comprises:

A) a biocatalyst immobilization chamber;

B) an input passage dimensioned for liquid communication between an input liquid transport line and said biocatalyst immobilization chamber; and

an output passage dimensioned for liquid communication between an output liquid transport line and said biocatalyst immobilization chamber.

15. The apparatus as claimed in claim 10, wherein a volume defined by said bioreactor chamber includes a truncated cone portion, a cylindrical portion, and a conical portion.

16. The apparatus as claimed in claim 15, wherein said truncated cone portion is disposed between said conical portion and said cylindrical portion.

17. The apparatus as claimed in claim 15, further including a machined conical recess that communicates with said cylindrical portion.