Device for cultivation of matrix-bound biologic cell systems

• US 4,373,029 A
• Filed: 08/21/1980
• Issued: 02/08/1983
• Est. Priority Date: 08/24/1979
• Status: Expired due to Term

• Current Assignee: Stephan Nees
• Original Assignee: Stephan Nees
• Inventors: Nees, Stephan
• Primary Examiner(s): Warden, Robert J.
• Application Number:
  US06/180,035
• Time in Patent Office: 901 Days
• Field of Search: 435/284, 435/285, 435/286, 366/208, 366/209, 366/214, 366/215, 366/216, 366/219, 366/232, 366/235
• US Class Current: 435/298.2
• CPC Class Codes: B01F 29/321 of test-tubes or the like
• CPC Class Codes: C12M 25/16 Particles; Beads; Granular material; Encapsulation chemical or physical processes conducted in the presence of fluids and solid particles B01J8/00
• CPC Class Codes: C12M 27/14 Rotation or movement of the cells support, e.g. rotated hollow fibers
• CPC Class Codes: C12M 27/16 Vibrating; Shaking; Tilting
• CPC Class Codes: C12N 1/00 Microorganisms, e.g. protozoa; Compositions thereof medicinal preparations containing material from protozoa, bacteria or viruses A61K35/66, from algae A61K36/02, from fungi A61K36/06; preparing medicinal bacterial antigen or antibody compositions, e.g. bacterial vaccines, A61K39/00; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor

Abstract

Improved apparatus for cultivation of matrix-bound biologic cell systems on microcarrier particles within a replenishable nutrient medium providing controlled three dimensional displacement of a culture vessel and its contents to effect uniform cell exposure to available nutrient material.

Claims

1. Apparatus for the cultivation of matrix-bound biologic cell systems on microcarrier particulates suspended in a nutrient medium comprising

a housing member having a longitudinal axis,

a culture vessel for containing said culture bearing microcarrier particulates in a nutrient medium removably insertable into said housing,

means for pivotally displacing said housing member and contained culture vessel through predetermined arcs in the vertical plane on either side of a reference base wherein said longitudinal axis of said housing member is disposed horizontal to ground,

means for rotatably displacing said housing member and contained culture vessel through a predetermined arc about said longitudinal axis in alternating clockwise and counterclockwise directions simultaneous with said pivotal displacement thereof.

2. Apparatus as set forth in claim 1 further including means for supporting a plurality of said housing members in spaced parallel relation for conjoint pivotal and rotational displacement thereof,

common drive means for effecting said pivotal and rotational displacement of said housing members including means for selectively varying the amounts of pivotal and rotational displacement thereof.

3. Apparatus as set forth in claim 2 wherein said common drive means further comprises

a rotatable shaft,

a crank arm connected to said shaft and rotatable therewith,

a first connecting rod connected to said crank arm and to said housing members supporting means for pivotally displacing the latter in response to crank arm rotation,

a second connecting rod connected to said crank arm and to said means for rotatably displacing said housing members for effecting rotational displacement of said housing members and contained culture vessels in response to crank arm rotation.

4. Apparatus as set forth in claim 3 wherein said means for rotationally displacing said housing members includes

intermeshed gear means associated with each of said housing members whereby rotation of one of said gears effects conjoint rotation of all of said gears and associated housing members,

and rack means connected to said second connecting rod and engageable with said gear means for converting induced lineal displacement of said rack means into rotational displacement of said housing members and contained culture vessels.

5. Apparatus as set forth in claim 1 further including

means for supporting a plurality of said housing members in spaced parallel relation for conjoint pivotal and rotational displacement thereof,

drive means for effecting said rotational displacement of said housing members including intermeshed gear means associated with each of said housing members whereby rotation of one of said gears effects conjoint rotation of all of said gears and associated housing members.

6. Apparatus as set forth in claim 1 further including

common drive means for effecting said pivotal and rotational displacement of said housing member and contained culture vessel comprising a rotatable shaft, a crank arm connected to said shaft and rotatable therewith, a first connecting rod connected to said crank arm for effecting said pivotal displacement of said housing member and contained culture vessel and a second connecting rod connected to said crank arm for effecting said rotational displacement of said housing member and contained culture vessel.

7. Apparatus as set forth in claim 6 further including

gear means associated with said housing member and

rack means connected to said housing connecting rod and engageable with said gear means for converting induced lineal displacement of said rack means into rotational displacement of said housing member and contained culture vessel.

8. Apparatus as set forth in claim 1 wherein said housing member comprises

a cylindrical body portion having one open end and

an elastic sleeve mounted on the open end thereof having an axial base sized to releasably and elastically engage a cylindrical culture vessel introducable therethrough.

9. Apparatus as set forth in claim 1 wherein said culture vessel comprises

a cylindrical tube having one open end and diametrically dimensioned to be contained within said housing member and further including

a closure head for the open end of said culture vessel containing at least two longitudinal bores therein for accommodation of nutrient feeding and nutrient removal conduits therein.

10. Apparatus as set forth in claim 9 wherein said nutrient feeding and nutrient removal conduits are disposed in flud communication with means to oxygenate and replenish said nutrient medium.

11. Apparatus as set forth in claim 9 including fluid filter means is interposed in the path of fluid removal through said nutrient removal conduit to prevent introduction of microcarrier particulates therein.

12. Apparatus as set forth in claim 1 wherein said culture vessel comprises

a cylindrical tube having one open end and diametrically dimensioned to be contained within said housing member and further including

a closure head for the open end of said culture vessel containing at least one longitudinal bore for accommodation of a fluid removal test conduit therein.

13. Apparatus as set forth in claim 1 wherein said culture vessel comprises a cylindrical tube of material impermeable to ultraviolet light.