BIOREACTOR WITH FILTRATION SYSTEMS

Claims

1. A perfusion device for cell culture, comprising: (a) a bioreactor vessel configured to contain a liquid medium containing a cell culture; (b) a first filtration unit in fluid communication with the bioreactor vessel, the first filtration unit comprising: (i) a first filtration system; (ii) a first collection pump connected in series with the first filtration system, wherein the first collection pump is configured to pump liquid medium from the bioreactor vessel through the first filtration system; and (iii) a sensor, wherein the sensor is configured to interact with the liquid medium in the first filtration unit; and (c) a second filtration unit configured to operate in parallel with the first filtration unit, wherein the second filtration unit is in fluid communication with the bioreactor vessel, and wherein the second filtration unit comprises: (i) a second filtration system; and (ii) a second collection pump connected in series with the second filtration system, wherein the second collection pump is configured to pump liquid medium from the bioreactor vessel through the second filtration system; and (d) a control device, wherein the control device performs operations including: (i) receiving from the sensor information indicating changes in the cell density in the first filtration system; (ii) determining, based on at least the received information from the sensor, whether the cell density in the first filtration system changes; and (iii) in response to detecting changes in cell density in the first filtration system, initiating a cessation of pumping by the first pump for collecting liquid medium through the first filtration system.

2. A perfusion device for culturing cells according to claim 1, characterized in that at least one of the first filtration system and the second filtration system comprises a filter with a variable tangential flow.

3. A perfusion device for culturing cells according to claim 1, characterized in that at least one of the first filtration system and the second filtration system comprises a tangential flow filter.

4. The perfusion device for culturing cells according to claim 1, characterized in that each of the first filtration system and the second filtration system contains a filter membrane containing a pore size from about 0.1 micron to about 1 micron.

5. The cell culture perfusion device of claim 1, wherein the sensor is an optical sensor, and wherein determining that the first change in cell density in the first filtration system comprises determining that the cell density in the first filtration unit is outside a predetermined threshold range.

6. A perfusion device for culturing cells according to claim 1, characterized in that the sensor detects an increase in cell density in the first filtration system.

7. A perfusion device for culturing cells according to claim 1, characterized in that the sensor detects a decrease in cell density in the first filtration system.

8. A perfusion device for culturing cells according to claim 1, characterized in that the control device is additionally configured to: in response to detecting a change in cell density in the first filtration system, initiating an increase by the second pump for collecting the flow rate of liquid medium through the second filtration system.

9. A perfusion device for culturing cells according to claim 8, characterized in that the initiation of an increase by the second pump for collecting the flow rate of liquid medium through the second filtration system includes approximately doubling the flow rate.

10. A perfusion device for culturing cells according to claim 1, characterized in that the control device is additionally configured to: in response to detecting changes in cell density in the first notification output filtering system.

11. The cell culture perfusion device of claim 10, wherein the notification includes a visible warning or an auditory warning.

12. A perfusion device for culturing cells according to claim 1, characterized in that it further comprises an isolation valve connected in series with the first filtration unit, wherein the valve is configured to control the flow of liquid medium through the first filtration unit, and wherein the control device is further configured to: in response to detecting changes in cell density in the first filtration system, closing the isolation valve.

13. A perfusion device for culturing cells according to claim 1, characterized in that the first filtration unit further comprises a protective filter connected in series with the first filtration system, wherein the protective filter is connected downstream relative to the first filtration system and the sensor.

14. The cell culture perfusion device of claim 13, wherein the protective filter has a pore size of from about 0.1 micron to about 1 micron.

15. A cell culture perfusion device according to claim 1, further comprising a capture operation adapted to collect a product from a liquid medium, wherein the capture operation is in fluid communication with the bioreactor vessel via at least a first filtration unit, and wherein the capture operation comprises multi-column chromatography (MCC).