Bioreactor Process Control System and Method

• US 20090104594A1
• Filed: 12/22/2005
• Published: 04/23/2009
• Est. Priority Date: 12/29/2004
• Status: Abandoned Application

• Current Assignee: Biogen Idec MA Inc. (Biogen, Inc.)
• Original Assignee: Biogen, Inc.
• Inventors: Webb, Marcus
• Application Number:
  US11/813,178
• Publication Number:
  US 20090104594A1
• Time in Patent Office: Days
• US Class Current: 435/3
• CPC Class Codes: C12M 41/48 Automatic or computerized control automatic analysis G01N35/00

Abstract

A bioreactor includes a sensor linked to a model free adaptive controller or optimizer. The sensor can provide a real time measurement of a quantity that correlates with final product titer or other desired product quality attribute.

Claims

1. A bioreactor comprising a cell growth vessel and a sensor;

wherein the sensor is configured to measure a condition inside the vessel and provide an input to a model-free adaptive controller.

2. The bioreactor of claim 1, wherein the sensor measures a condition that correlates with a product quality attribute.

3. The bioreactor of claim 2, wherein the product quality attribute is final product titer.

4. The bioreactor of claim 2, wherein the sensor is configured to provide the input in real time.

5. The bioreactor of claim 4, wherein the sensor measures viable cell density directly or indirectly.

6. The bioreactor of claim 1, wherein the model-free adaptive controller is configured to compare the input to a setpoint.

7. The bioreactor of claim 1, wherein the model-free adaptive controller is configured to provide an output to an actuator.

8. The bioreactor of claim 1, wherein the sensor is configured to measure viable cell density, temperature, agitation speed, dissolved oxygen, pH, turbidity, conductivity, pressure, NO/NOx, TOC/VOC, chlorine, ozone, oxidation-reduction potential, viscosity or suspended solids.

9. The bioreactor of claim 1, wherein the sensor is configured to measure the condition using a method selected from the group consisting of:

electrochemical, infrared, optical chemical, radar, vision, radiation, pulse dispersion and mass spectrometry, acoustics, tomography, gas chromatography, liquid chromatography, spectrophotometry, opacity, thermal conductivity, refractometry, and strain.

10. The bioreactor of claim 1, further comprising a second sensor configured to measure a second condition inside the vessel and provide a second input to the model-free adaptive controller.

11. A method of culturing living cells comprising:

incubating the cells in a vessel;

measuring a condition inside the vessel;

comparing the measurement to a setpoint with a model-free adaptive controller; and

adjusting a condition inside the vessel based on the comparison.

12. The method of claim 11, wherein the condition is viable cell density, temperature, agitation speed, dissolved oxygen, pH, turbidity, conductivity, pressure, NO/NOx, TOC/VOC, chlorine, ozone, oxidation-reduction potential, viscosity or suspended solids.

13. The method of claim 11, wherein measuring a condition includes using a method selected from the group consisting of:

electrochemical, infrared, optical chemical, radar, vision, radiation, pulse dispersion and mass spectrometry, acoustics, tomography, gas chromatography, liquid chromatography, spectrophotometry, opacity, thermal conductivity, refractometry, and strain.

14. The method of claim 11, wherein the condition is a condition that correlates with a product quality attribute.

15. The method of claim 14, wherein the product quality attribute is final product titer.

16. The method of claim 14, wherein measuring a condition includes measuring in real time.

17. The method of claim 15, wherein measuring a condition includes measuring the viable cell density.

18. The method of claim 11, further comprising adjusting the setpoint.

19. The method of claim 18, wherein the setpoint is adjusted according to a predetermined trajectory.

20. A method of culturing living cells comprising:

incubating the cells in a vessel;

measuring a plurality of conditions inside the vessel;

comparing the plurality of measurements, individually, to a plurality of setpoints with a model-free adaptive controller; and

adjusting a first condition inside the vessel based on at least one comparison.

21. The method of claim 20, wherein at least one measured condition is viable cell density, temperature, agitation speed, dissolved oxygen, pH, turbidity, conductivity, pressure, NO/NOx, TOCNVOC, chlorine, ozone, oxidation-reduction potential, viscosity or suspended solids.

22. The method of claim 20, wherein measuring a plurality of conditions includes using a method selected from the group consisting of:

electrochemical, infrared, optical chemical, radar, vision, radiation, pulse dispersion and mass spectrometry, acoustics, tomography, gas chromatography, liquid chromatography, spectrophotometry, opacity, thermal conductivity, refractometry, and strain.

23. The method of claim 20, further comprising adjusting a plurality of conditions inside the vessel based on at least one comparison.

24. The method of claim 20, wherein at least one measured condition is a condition that correlates with a product quality attribute.

25. The method of claim 24, wherein the product quality attribute is final product titer.

26. The method of claim 24, wherein at least one measured condition is measured in real time.

27. The method of claim 26, wherein viable cell density is measured in real time.

28. The method of claim 20, further comprising adjusting at least one setpoint.

29. The method of claim 28, wherein the setpoint is adjusted according to a predetermined trajectory.

30. A bioreactor comprising:

a cell growth vessel;

a sensor configured to measure a condition inside the vessel, wherein the condition correlates with final product titer; and

a model-free adaptive controller configured to receive a measurement from the sensor and provide an output to an actuator.

31. The bioreactor of claim 30, wherein the sensor is configured to measure viable cell density.

32. The bioreactor of claim 30, wherein the sensor is configured to measure the condition in real time.

33. A method of selecting conditions for a bioreactor process comprising:

incubating a plurality of cells in a vessel;

measuring a plurality of conditions inside the vessel; and

determining a preferred level of a selected condition with a model-free adaptive controller.

34. The method of claim 33, wherein determining a preferred level of a selected condition includes determining an optimum level of the condition.