Granted Patent B2

US 12,497,586 · App. 17/763,860 · Granted Dec 16, 2025

Inventors: Shivakumar Selvaraj (Bengaluru, IN); Bineesh Kandoth (Bengaluru, IN); Sahebagouda Alagur (Bengaluru, IN); Nagaraj Raghavendra Rao (Bengaluru, IN); Thomas Falkman (Uppsala, SE)

Assignee: CYTIVA SWEDEN AB

C12M41/48C12M29/06C12M41/34

Abstract

Claims (49)

1 . A bioreactor apparatus, comprising:

a bioreactor vessel configured to culture cells;

a sensor configured to measure Dissolved Oxygen (DO) in the bioreactor vessel; and

a controller configured to:

obtain the DO measurements, the DO measurements comprising a plurality of DO values recorded at, at least, a plurality of time instances during operation of the bioreactor apparatus;

determine, in real-time, an oxygen mass transfer co-efficient (kLa) associated with the operation of the bioreactor apparatus; and

control, in real-time, at least one cell culture parameter associated with the operation of the bioreactor apparatus based on the kLa.

2 . The bioreactor apparatus of claim 1 , wherein the controller is further configured to:

determine a plurality of log values based on the plurality of DO values and the plurality of time instances; and

determine, in real-time, the kLa based on the plurality of log values.

3 . The bioreactor apparatus of claim 1 , wherein the bioreactor apparatus further comprises a sparger coupled with the bioreactor vessel, wherein the at least one cell culture parameter is the DO, wherein the controller is configured to:

compare a value of kLa with a preset value of kLa; and

control an operational speed of the sparger for controlling a flow rate of input oxygen into the bioreactor vessel, when the value of the kLa is different from the preset value of the kLa.

4 . The bioreactor apparatus of claim 1 , wherein the controller is further configured to:

compare, in real-time, the DO measurements with historic DO measurements, wherein the historic DO measurements comprises a plurality of DO values recorded during previous operations of the bioreactor apparatus;

detect an anomaly associated with the DO based on the comparison of the DO measurements with the historic DO measurements; and

provide an alert notification in response to the detection of the anomaly.

5 . The bioreactor apparatus of claim 1 , wherein the controller is further configured to:

compare, in real-time, the DO measurements with a predetermined threshold DO range;

determine that a real-time value of the DO is outside the predetermined threshold DO range; and

provide an alert notification in response to the determining that the real-time value of the DO is outside the predetermined threshold DO range.

6 . The bioreactor apparatus of claim 1 , wherein the bioreactor apparatus further comprises a display unit, wherein the controller is further configured to display the kLa through the display unit.

7 . The bioreactor apparatus of claim 6 , wherein the controller is further configured to:

compare, in real-time, the DO measurements with historic DO measurements, wherein the historic DO measurements comprises a plurality of DO values recorded during previous operations of the bioreactor apparatus;

determine a comparative graph based on the comparison, wherein the comparative graph is indicative of a performance of a current operation in comparison to historic operations of the bioreactor apparatus; and

display the comparative graph using the display unit.

8 . A method of operating a bioreactor apparatus, the method comprising:

measuring, by a sensor, Dissolved Oxygen (DO) present in a bioreactor vessel of the bioreactor apparatus during an operation of the bioreactor apparatus, wherein DO measurements comprise a plurality of DO values recorded at, at least, a plurality of time instances during the operation of the bioreactor apparatus;

determining, in real-time, by a controller, an oxygen mass transfer co-efficient (kLa) associated with the operation of the bioreactor apparatus; and

controlling, in real-time, by the controller, at least one cell culture parameter associated with the operation of the bioreactor apparatus based on the kLa.

9 . The method as claimed in claim 8 , wherein the step of determining further comprises:

determining a plurality of log values based on the plurality of DO values and the plurality of time instances; and

determining, in real-time, the kLa based on the plurality of log values.

10 . The method as claimed in claim 8 , wherein the bioreactor apparatus further comprises a sparger coupled with the bioreactor vessel, wherein the at least one cell culture parameter is DO, wherein the method further comprises:

comparing a value of kLa with a preset value of kLa; and

controlling an operational speed of the sparger for controlling a flow rate of input oxygen into the bioreactor vessel, when the value of the kLa is different from the preset value of the kLa.

11 . The method as claimed in claim 8 , wherein the method further comprises:

comparing, in real-time, the DO measurements with historic DO measurements, wherein the historic DO measurements comprises a plurality of DO values recorded during previous operations of the bioreactor apparatus;

detecting an anomaly associated with the DO based on the comparison of the DO measurements with the historic DO measurements; and

providing an alert notification in response to the detection of the anomaly.

12 . The method as claimed in claim 8 , wherein the method further comprises:

comparing, in real-time, the DO measurements with a predetermined threshold DO range;

determining that a real-time value of the DO is outside the predetermined threshold DO range; and

providing an alert notification in response to the determining that the real-time value of the DO is outside the predetermined threshold DO range.

13 . The method as claimed in claim 8 , wherein the method further comprises displaying the kLa through a display unit.

14 . The method as claimed in claim 13 , wherein the method further comprises:

comparing, in real-time, the DO measurements with historic DO measurements, wherein the historic DO measurements comprises a plurality of DO values recorded during previous operations of the bioreactor apparatus;

determining a comparative graph based on the comparison, wherein the comparative graph is indicative of a performance of the operation in comparison to historic operations of the bioreactor apparatus; and

displaying the comparative graph using the display unit.

Assignments (2)

Priority Claims (1)

Continuity (1)

References Cited (14)