Particle settler for use in cell culture

• US 5,817,505 A
• Filed: 11/07/1995
• Issued: 10/06/1998
• Est. Priority Date: 05/07/1993
• Status: Expired due to Term

• Current Assignee: Millipore UK Ltd (Merck & Co., Inc.)
• Original Assignee: Bioscot Limited
• Inventors: Wilson, James Samuel, Thompson, Keith John
• Primary Examiner(s): Redding, David A.
• Application Number:
  US08/545,712
• Time in Patent Office: 1,064 Days
• Field of Search: 435/286.1, 435/289.1, 435/308.1, 435/819, 435/813, 210/800, 210/801, 210/802, 210/513, 210/521, 210/383, 210/393, 210/394
• US Class Current: 435/286.1
• CPC Class Codes: B01D 21/0015 Controlling the inclination of settling devices
• CPC Class Codes: B01D 21/0039 Settling tanks provided with contact surfaces, e.g. baffles, particles
• CPC Class Codes: B01D 21/0045 Plurality of essentially parallel plates
• CPC Class Codes: B01D 21/0057 with counter-current flow direction of liquid and solid particles
• CPC Class Codes: B01D 21/009 Heating or cooling mechanisms specially adapted for settling tanks
• CPC Class Codes: B01D 21/2488 bringing about a partial recirculation of the liquid, e.g. for introducing chemical aids
• CPC Class Codes: B01D 2221/10 Separation devices for use in medical, pharmaceutical or laboratory applications, e.g. separating amalgam from dental treatment residues
• CPC Class Codes: C12M 33/22 Settling tanks; Sedimentation by gravity settling tanks per se B01D21/02
• CPC Class Codes: Y10S 435/813 Continuous fermentation

Abstract

Disclosed is a device for separating particles from a bulk liquid, such as viable hybridoma cells from antibody-containing liquid medium. The device comprises a plurality of settlement plates, or other surfaces, being inclined to the vertical, and a pump or other means for causing liquid containing the particles to flow upwardly over the surfaces at such a rate as to allow particles to be separated from the bulk liquid to form sediment layers on the surfaces and slide down them for collection at an appropriate point.

Claims

1. A device for separating particles from a bulk liquid under aseptic or sterile conditions, the device comprising means defining a plurality of settlement surfaces, the surfaces being inclined to the vertical, and means for causing liquid containing the particles to flow upwardly over said surfaces at such a rate as to allow particles to be separated from the bulk liquid to form sediment layers on the surfaces and slide down them, wherein said surfaces and said means for causing the liquid to flow upwards are contained within a sterile housing.

2. A device as claimed in claim 1, comprising at least fifteen settlement surfaces.

3. A device as in claim 1, wherein the means defining the settlement surfaces are plates.

4. A device as claimed in claim 3, wherein at least the uppermost surface of each plate is formed of mirror-polished stainless steel.

5. A device as claimed in claim 3, wherein the spacing between the plates is from 0.2 cm and 2 cm.

6. A device as claimed in claim 1, wherein the angle at which the surfaces are inclined to the vertical is from 10°

to 50°

.

7. A device as claimed in claim 1, wherein said vertically inclined settlement surfaces are mounted on a means for adjusting the angle of said incline, whereby the angle at which the surfaces are inclined to the vertical is adjustable.

8. A device as claimed in claim 7, wherein said means for adjusting the angle of said incline is an adjustable stand.

9. A device as claimed in claim 1, wherein the device is capable of being used at a liquid flow rate of from 0.5 to 5 dm³ /h.

10. A device as claimed in claim 1, wherein said housing is provided with an inlet for liquid containing particles to be separated, an outlet for liquid from which particles have been separated and a collection outlet for separated particles.

11. A device as claimed in claim 1, wherein the means for causing the liquid to flow upwardly over the settlement surfaces is a pump.

12. A device as claimed in claim 11, wherein the pump is capable of intermittent operation.

13. A device as claimed in claim 11, wherein the flow of liquid through the pump is capable of being periodically reversed.

14. A device as claimed in claim 1, said device further comprising temperature control means to keep the temperature of the liquid in the device within predetermined limits.

15. A device as claimed in claim 1, said device further comprising a collection outlet for removal of viable or total hybridoma cells from cell-containing medium.

16. A bioreactor apparatus, the apparatus comprising a fermenter vessel adapted to contain cells in liquid culture, and a device as claimed in claim 1 for operation under aseptic or sterile conditions, the device being so coupled to the fermenter vessel to allow cells, or a population of cells, in the liquid medium to be separated from liquid medium and returned to the fermenter vessel.

17. An apparatus as claimed in claim 16 wherein the fermenter is a stirred tank or airlift fermenter.

18. An apparatus as claimed in claim 16, which contains mammalian cells in liquid culture.

19. A process for separating particles from a bulk liquid under aseptic or sterile conditions, the process comprising causing liquid containing the particles to flow upwardly over a plurality of settlement surfaces, the surfaces being inclined to the vertical, at such a rate as to allow particles to be separated from the bulk liquid to form sediment layers on the surfaces and slide down them, said process carried out in the apparatus of claim 1.

20. A process as claimed in claim 19, wherein there are at least fifteen settlement surfaces.

21. A process as claimed in claim 19, wherein the settlement surfaces are defined by plates.

22. A process as claimed in claim 21, wherein at least the uppermost surface of each plate is formed of mirror-polished stainless steel.

23. A process as claimed in claim 21, wherein the spacing between the plates is from 0.2 cm and 2 cm.

24. A process as claimed in claim 19, wherein the angle at which the surfaces are inclined to the vertical is from 10°

to 50°

.

25. A process as claimed in claim 19, wherein said vertically inclined settlement surfaces are mounted on a means for adjusting the angle of said incline, whereby the angle at which the surfaces are inclined to the vertical is adjustable.

26. A process as claimed in claim 19, wherein the liquid flow rate is from 0.5 to 5 dm³ /h.

27. A process as claimed in claim 19, wherein the surfaces are contained in a housing provided with an inlet for liquid containing particles to be separated, an outlet for liquid from which particles have been separated and a collection outlet for separated particles.

28. A process as claimed in claim 19, wherein the liquid is caused to flow upwardly over the settlement surfaces by a pump.

29. A process as claimed in claim 19 wherein the temperature of liquid is kept within predetermined limits.

30. A process as claimed in claim 19 which comprises removing viable or total hybridoma cells from cell-containing medium.

31. A process of claim 19, wherein said bulk liquid is a liquid medium wherein mammalian cells are cultured.