Bioreactor system with plasticizer removal

• US 4,918,019 A
• Filed: 02/05/1987
• Issued: 04/17/1990
• Est. Priority Date: 05/12/1986
• Status: Expired due to Fees

• Current Assignee: CD Medical Incorporated (Baxter International Inc.)
• Original Assignee: C.P. Medical Corporation (Riverpoint Medical Llc)
• Inventors: Guinn, Perry W.
• Primary Examiner(s): Richman, Barry S.
• Assistant Examiner(s): McMahon, Timothy M.
• Application Number:
  US07/011,913
• Time in Patent Office: 1,167 Days
• Field of Search: 435/240.2, 435/240.21, 435/244, 435/287, 435/289, 435/311, 435/313, 435/803, 435/811, 435/820
• US Class Current: 435/286.5
• CPC Class Codes: A61M 1/3475 with filtrate treatment agent in the same enclosure as the membrane
• CPC Class Codes: A61M 1/3489 by biological cells, e.g. bioreactor
• CPC Class Codes: C12M 23/42 Integrated assemblies, e.g. cassettes or cartridges
• CPC Class Codes: C12M 29/12 Pulsatile flow
• CPC Class Codes: C12M 29/16 Hollow fibers hollow fiber modules in general B01D63/02
• CPC Class Codes: C12M 37/00 Means for sterilizing, maintaining sterile conditions or avoiding chemical or biological contamination C12M23/38 takes precedence; filtration in general and filters per se B01D24/00-B01D41/00; autoclaves B01J3/04; treatment of microorganisms with electrical or wave energy C12N13/00
• CPC Class Codes: Y10S 435/803 Physical recovery methods, e.g. chromatography, grinding
• CPC Class Codes: Y10S 435/811 Interferon
• CPC Class Codes: Y10S 435/82 Subcellular parts of microorganisms

Abstract

An improved hollow fiber bioreactor system is disclosed that includes an arrangement for removing the plasticizer that is typically found within the hollow fibers of hollow fiber cartridges so as to prevent this material from contaminating the nutrient fluid. The plasticizer is removed without jeopardizing sterility of the bioreactor.

Claims

1. A bioreactor system comprising:

reservoir means for containing nutrient fluid, said reservoir means having first and second ports;

bioreactor means including a plurality of semipermeable fibers for containing cells to be nourished by the nutrient fluid, said bioreactor means having first and second nutrient flow ports;

fluid circuit means for allowing the circulation of nutrient fluid from the reservoir means through the bioreactor means, said fluid circuit means including a first portion coupling the first port of the reservoir means to the first nutrient fluid flow port of the bioreactor means, said fluid circuit means including a second portion coupling the second port of the reservoir means to the second nutrient fluid flow port of the bioreactor means;

recirculation means including a first pump for driving the nutrient fluid through the fluid circuit means; and

means for flushing manufacturing residue from the bioreactor means while maintaining system sterility, said means comprising;

a waste fluid outlet port;

a sterile fluid source;

a second pump means having an inlet coupled to the sterile fluid source and an outlet coupled to the second portion of the fluid circuit means, said second pump means being distinct from the first pump, for introducing sterile fluid from the sterile fluid source into the second portion of the fluid circuit means;

first valve means in the second portion of the fluid circuit means for isolating the sterile fluid source and the second nutrient fluid flow port of the bioreactor means from the second port of the reservoir means when in a first state, said valve means coupling the second nutrient fluid flow port of the bioreactor means to the second port of the reservoir means when in a second state;

second valve means for coupling the first nutrient fluid flow port of the bioreactor means to the waste fluid outlet port when in a first state, said second valve means isolating the first nutrient fluid flow port from the waste fluid outlet port when in a second state;

third valve means for isolating the first nutrient fluid flow port of the reservoir means from the first port of the reservoir means when in a first state, said third valve means coupling the first nutrient fluid flow port to the first port of the reservoir means when in a second state;

whereby when said valves are in their first state, sterile fluid introduced into the second portion of the fluid circuit means by the second pump means flows into the second nutrient fluid flow port of the bioreactor means and out the first nutrient fluid flow port of the bioreactor means to the waste fluid outlet port, thereby flushing manufacturing residue from the bioreactor means to the waste fluid outlet port, and when said valves are thereafter switched to their second states, the nutrient fluid is able to circulate from the reservoir means through the bioreactor means in an isolated loop free from manufacturing residue initially present in the bioreactor means.

2. A bioreactor system comprising:

reservoir means for containing nutrient fluid, said reservoir means having first and second ports;

bioreactor means including a plurality of semipermeable fibers for containing cells to be nourished by the nutrient fluid, said bioreactor means having first and second nutrient ports;

fluid circuit means for allowing the circulation of the nutrient fluid from the reservoir means through the bioreactor means, said fluid circuit means including a first portion coupling the first port of the reservoir means to the first nutrient port of the bioreactor means, said fluid circuit means including a second portion coupling the second port of the reservoir means to the second nutrient port of the bioreactor means;

recirculation means including a first pump for driving the nutrient fluid through the fluid circuit means; and

priming means coupled to the fluid circuit means and to the bioreactor means and having first and second operational states, for flushing manufacturing residue from the bioreactor means and out of the fluid circuit means without contaminating the reservoir means with said residue when said means is in the first operational state and for isolating the fluid circuit means from the flushed residue when said means is in the second operational state, said priming means including a second pump distinct from the first, said second pump having an inlet coupled to a source of flush fluid and having an outlet coupled to the fluid circuit means, for urging flush fluid into the fluid circuit to flush the manufacturing residue from the bioreactor means.

3. The system of claim 2 in which said last mentioned means comprises:

a waste fluid outlet port;

a sterile fluid source;

means for coupling a flow of sterile fluid from the sterile fluid source into the second nutrient port of the bioreactor means;

valve means interposed in the first portion of the fluid circuit means and having first and second operational states for;

isolating the first nutrient port of the bioreactor means from the first port of the reservoir means and coupling said first nutrient port to the waste fluid outlet port when in the first operational state; and

coupling the first nutrient port of the bioreactor means to the first port of the reservoir means and isolating said first nutrient port from the waste fluid outlet port when in the second operational state,

whereby when said valve means is in its first state, sterile fluid introduced into the second nutrient port of the bioreactor means flows out the first nutrient port of the bioreactor means and to the waste fluid outlet port, thereby flushing manufacturing residue from the bioreactor means and out the fluid circuit means to the waste fluid outlet port, and when said valve means is thereafter switched to its second state, nutrient fluid can circulate from the reservoir means through the fluid circuit means and the bioreactor means in an isolated loop free from manufacturing residue initially present in the bioreactor means.

4. The system of claim 3 in which the sterile fluid source comprises a source of nutrient fluid.

5. The system of claim 3 in which the second portion of the fluid circuit means includes second valve means for isolating the sterile fluid source and the second nutrient port of the bioreactor means from the second port of the reservoir means when said second valve is in a first state, said second valve means coupling the second nutrient port of the bioreactor means to the second port of the reservoir means when in a second state.

6. The system of claim 3 which further includes a pump means interposed between the first nutrient port of the bioreactor means and the waste fluid outlet port for drawing sterile fluid from the sterile fluid source, through the bioreactor means and out to the waste fluid outlet port.

7. The system of claim 6 in which said pump means is included in the first portion of the fluid circuit means.

8. The system of claim 6 in which the means for introducing sterile fluid from the sterile fluid source into the second portion of the fluid circuit means comprises a feed pump including a removable pump segment.

9. The system of claim 6 in which the recirculation means includes the pump means.

10. The system of claim 3 which additionally comprises a semipermeable membrane oxygenator serially connected with the bioreactor means between the first and second portions of the fluid circuit means.

11. The system of claim 3 which further comprises means for selectively isolating the sterile fluid source from the second nutrient port of the bioreactor means.