Patent ID: 11965153
Assignee: REGENERON PHARMACEUTICALS, INC.
Field: Biotechnology (Chemistry)
Classification: CPC C | IPC C

Claim 16:
17. A method of controlling a bioreactor system, comprising:
providing a cell culture in a perfusion bioreactor;
measuring one or more process parameters of the cell culture by a RAMAN probe;
removing cell-free spent media from the cell culture using a first output conduit at a first specified rate;
removing cells from the cell culture using a second output conduit at a second specified rate;
introducing one or both of fresh media or nutrients into the cell culture using an input conduit at a third specified rate;
determining a first change to one or more of the first specified rate, the second specified rate, or the third specified rate based on the RAMAN probe measurements; and
applying a second change to another one of the first specified rate, the second specified rate, or the third specified rate in response to the first change to maintain a perfusion rate through the bioreactor system substantially constant such that a total input and a total output of the perfusion bioreactor remains substantially constant during the first change and the second change;
wherein the input and output conduits are automatically adjusted, by a controller receiving the RAMAN probe measurements, to maintain (i) one or more of the process parameters within predetermined ranges, (ii) the first specified rate and the second specified rate of each of the output conduits within respective predetermined ranges, (iii) the third specified rate of the input conduit within a predetermined range, and (iv) the perfusion rate of the perfusion bioreactor based on a constant perfusion rate setpoint.