Bioreactor apparatus and operation method thereof

Patent metadata

Field	Value
Publication number	US-12497586-B2
Application number	US-202017763860-A
Country	US
Kind code	B2
Filing date	Oct 1, 2020
Priority date	Oct 11, 2019
Publication date	Dec 16, 2025
Grant date	Dec 16, 2025

Abstract

The present subject matter discloses a bioreactor apparatus. The bioreactor apparatus comprises a bioreactor vessel configured to culture cells. The bioreactor apparatus furthermore comprises a sensor configured to measure Dissolved Oxygen (DO) in the bioreactor vessel. The DO measurements comprise a plurality of DO values recorded at, at least, a plurality of time instances during operation of the bioreactor apparatus. The bioreactor apparatus furthermore comprises a controller configured to obtain the DO measurements. The controller furthermore is to determine, in real-time or approximately real-time, an oxygen mass transfer co-efficient (kLa) associated with the operation of the bioreactor apparatus. Furthermore, the controller is configured to control, in real-time or approximately real-time, at least one cell culture parameter associated with the operation of the bioreactor apparatus based on the kLa.

First claim

We claim:

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.

Assignees

• Cytiva Sweden Ab

Inventors

• Selvaraj Shivakumar
• Kandoth Bineesh
• Alagur Sahebagouda
• Rao Nagaraj Raghavendra
• Falkman Thomas

Classifications

• C12M41/34 Primary

  of gas · CPC title

• C12M29/06

  Nozzles; Sprayers; Spargers; Diffusers (per se B01F23/231, B01J19/26) · CPC title

• C12M41/48 Primary

  Automatic or computerized control (automatic analysis G01N35/00) · CPC title

• C12M41/32 Primary

  of substances in solution · CPC title