Automated cell culture and testing system

• US 5,424,209 A
• Filed: 03/19/1993
• Issued: 06/13/1995
• Est. Priority Date: 03/19/1993
• Status: Expired due to Fees

• Current Assignee: Continuus Properzi SPA
• Original Assignee: George P. Kearney
• Inventors: Kearney, George P.
• Primary Examiner(s): Beisner, William H.
• Application Number:
  US08/034,542
• Time in Patent Office: 816 Days
• Field of Search: 435/3, 435/284-286, 435/289, 435/290, 435/316, 435/809, 422/100, 222/103, 222/214
• US Class Current: 435/286.5
• CPC Class Codes: C12M 23/42 Integrated assemblies, e.g. cassettes or cartridges
• CPC Class Codes: C12M 23/58 Reaction vessels connected in series or in parallel combinations of bioreactors with other apparatus, C12M43/00
• CPC Class Codes: C12M 29/26 Conditioning fluids entering or exiting the reaction vessel
• CPC Class Codes: C12M 41/14 Incubators; Climatic chambers per se B01L1/00
• CPC Class Codes: C12M 41/18 Heat exchange systems, e.g. heat jackets or outer envelopes
• CPC Class Codes: C12M 41/48 Automatic or computerized control automatic analysis G01N35/00
• CPC Class Codes: Y10S 435/809 Incubators or racks or holders for culture plates or containers

Abstract

A cell culture and testing system provides a completely self-contained environment in which living tissues may be placed and where living tissues may be nutrified, oxygenated and maintained within a range of temperatures within which life may be sustained. The system includes aspects permitting administering of drugs or other substances to living tissues and monitoring of results accruing from such administration. In the preferred embodiment, the system is completely self-contained and sealed and may be operated both through use of an external power supply and an internal back-up power supply. The system is maintained at a positive pressure slightly above atmospheric pressure to prevent contamination from the surrounding environment. The system includes at least three levels of containment to completely isolate living tissues from ambient surroundings and the system has been successfully tested under conditions of zero gravity.

Claims

1. A self-contained cell culture and testing system, comprising:

a) a housing defining a sealed chamber sealed against any incursions;

b) a plurality of culture systems independently contained within said chamber, each culture system including;

i) a plurality of bioreactors for containing living cells, each bioreactor including a bioreactor inlet and a bioreactor outlet;

ii) first supply means for supplying nutrition media or tissue testing media to each of said bioreactor inlets;

iii) exhaust means for exhausting spent media from each of said bioreactor outlets, said exhaust means including second supply means for supplying said spent media to either a sump or a collection chamber;

iv) a plurality of fluid pathways, said bioreactor inlet and outlet of each bioreactor being in fluid communication with one of said plurality of fluid pathways such that parallel and non-communicating flow is provided between said first supply means and said exhaust means;

v) a plurality of recirculation pathways, each bioreactor including one of said plurality of recirculation pathways for recirculating said spent media from said bioreactor outlet back to said bioreactor inlet;

vi) oxygenation means for oxygenating said spent media in said plurality of recirculation pathways with oxygen containing gas, said oxygenation means comprising a single canister oxygenator including a discrete separate oxygenating path for each recirculation pathway, each said discrete separate oxygenating path including means for introduction of gas to said spent media in a direction countercurrent to a direction of flow of said spent media;

vii) said exhaust means including first valve means for providing selective flow of said spent media from each bioreactor outlet to said plurality of recirculation pathways or to said second supply means;

viii) said first supply means including second valve means for providing selective flow of nutrition media or tissue testing media to said plurality of bioreactors;

ix) said second supply means including third valve means for providing selective flow of said spent media to said sump or to said collection chamber;

x) thermal control means for controlling temperature of said plurality of bioreactors, said media, and said gas, said thermal control means including a solid metallic heat sink including a heater/cooler mounted directly thereto, said plurality of bioreactors and said oxygenation means being mounted in said heat sink;

c) a gas pathway including gas supply means for supplying filtered humidified temperature controlled gas to said oxygenation means of each culture system, and gas exhaust means for exhausting spent gasses from said sealed chamber;

d) computer means including sensing means for sensing heat sink temperature and media pH in each culture system; and

control means for controlling position of said first, second and third valve means, and for controlling operation of said thermal control means, said first supply means and said recirculation means of each culture system whereby living cells within said plurality of bioreactors are maintained nourished, oxygenated and within life sustaining temperature limits.

2. The system of claim 1, wherein said sealed chamber is completely contained within a further sealed chamber.

3. The system of claim 1, wherein said first supply means includes a pump.

4. The system of claim 3, wherein said first supply means further includes a container for said nutrition media.

5. The system of claim 4, wherein said first supply means further includes at least one further container for said tissue testing media.

6. The system of claim 5, wherein said container and said at least one further container each comprises a flexible container surrounded by an elastic pressurizing sleeve.

7. The system of claim 5, wherein said second valve means is located upstream of said pump.

8. The system of claim 1, wherein said collection chamber comprises one of a plurality of collection chambers, and further including a manifold downstream of said third valve means and control means associated with said manifold for permitting choosing one of said plurality of collection chambers for receipt of said spent media from said exhaust means.

9. The system of claim 1, wherein said recirculation pathways include a recirculation pump.

10. The system of claim 9, wherein said recirculation pump comprises a single peristaltic-type pump in communication with each recirculation pathway.

11. The system of claim 1, wherein said gas supply means maintains pressure in said sealed chamber above ambient pressure.

12. The system of claim 1, further including a plurality of rail assemblies, each rail assembly supporting one of said plurality of culture systems.

13. The system of claim 1, wherein said heater/cooler comprises a Peltier-type heater/cooler.

14. The system of claim 13, wherein said sensing means includes a temperature sensor embedded in said heat sink of each culture system.

15. The system of claim 1, wherein said computer means includes a main computer and a plurality of controllers connected to said main computer, each of said controllers controlling preassigned system functions under control of said main computer.

16. The system of claim 1, wherein said first, second and third valve means of each culture system are each solenoid operated by said computer means.