Granted Patent B2

US 12,516,280 · App. 16/741,044 · Granted Jan 6, 2026

Inventors: Brandon Berry (Boston, MA); Justin Moretto (Apex, NC)

Assignee: Biogen MA Inc.

C12M41/32C12M41/48G01N21/65G01N2201/12

Abstract

Claims (33)

1 . A method of assessing a bioreactor culture, the method comprising:

(i) obtaining a Raman spectrum of a manufacturing-scale bioreactor culture using a probe configured inline with the bioreactor; and

(ii) determining a culture parameter of the manufacturing-scale bioreactor culture using a model that relates the Raman spectrum to the culture parameter, wherein the model is developed based on one or more test bioreactor cultures of a smaller volume than the manufacturing-scale bioreactor culture;

wherein the volume of the manufacturing-scale bioreactor culture is in a range of 1000 L to 100,000 L.

2 . The method of claim 1 , wherein the volume of the manufacturing-scale bioreactor culture is in a range of 1000 L to 4000 L.

3 . The method of claim 1 , wherein the volume of the test bioreactor culture is in a range of 1 L to 400 L.

4 . The method of claim 1 , wherein the model is a partial least squares model.

5 . The method of claim 1 , wherein the culture parameter is a level of glucose, glutamate, ammonia or lactate in the culture.

6 . The method of claim 1 , wherein the culture parameter is the osmolality of the culture.

7 . A method of assessing a bioreactor culture, the method comprising:

(i) obtaining a Raman spectrum of a manufacturing-scale bioreactor culture using a probe configured inline with the bioreactor; and

(ii) determining a culture parameter of the manufacturing-scale bioreactor culture using a model that relates the Raman spectrum to the culture parameter, wherein the model is developed based on at least one bioreactor culture of a smaller volume than the manufacturing-scale bioreactor culture and at least one bioreactor culture of substantially the same volume as the manufacturing-scale bioreactor culture;

wherein the volume of the manufacturing-scale bioreactor culture is in a range of 1000 L to 100,000 L.

8 . The method of claim 7 , wherein the manufacturing-scale bioreactor culture is in a range of 1000 L to 4000 L.

9 . The method of claim 7 , wherein the at least one bioreactor culture of a smaller volume than the manufacturing-scale bioreactor culture is in a range of 1 L to 100 L.

10 . The method of claim 7 , wherein the Raman spectrum comprises spectral signal in the 200 cm −1 to 3400 cm −1 wavenumber range.

11 . The method of claim 7 , wherein the Raman spectrum is obtained using a Raman analyzer configured with a laser or other suitable light source that operates at wavelengths in a range of 325 nm to 1064 nm.

12 . A bioreactor system comprising:

a bioreactor chamber configured for containing a manufacturing-scale bioreactor culture;

a probe configured inline with the bioreactor chamber for obtaining a Raman spectrum of the manufacturing-scale bioreactor culture; and

a computer configured for determining a culture parameter of the manufacturing-scale bioreactor culture, wherein the computer comprises:

an input interface configured to receive information indicative of the Raman spectrum obtained from the probe;

at least one processor programmed to evaluate a model that relates the Raman spectrum to the culture parameter, wherein the model is developed based on one or more test bioreactor cultures of a smaller volume than the manufacturing-scale bioreactor culture, and

an output interface configured to output a signal indicative of the determined culture parameter;

wherein the volume of the manufacturing-scale bioreactor culture is in a range of 1000 L to 100,000 L.

13 . The bioreactor system of claim 12 , wherein the output comprises a feedback control signal for controlling operation of a device for altering the culture parameter.

14 . The bioreactor system of claim 13 , wherein the device for altering the culture parameter is a pump or valve that controls flow, into or out from the bioreactor culture, of a medium comprising one or more culture components.

15 . The bioreactor system of claim 12 , wherein the volume of the manufacturing-scale bioreactor culture is in a range of 1000 L to 4000 L.

16 . The bioreactor system of claim 12 , wherein the volume of the test bioreactor culture is in a range of 1 L to 400 L.

17 . The bioreactor system of claim 12 , wherein the model is a partial least squares model.

18 . The bioreactor system of claim 12 , wherein the culture parameter is a level of glucose, glutamate, ammonia or lactate in the culture.

19 . The bioreactor system of claim 12 , wherein the culture parameter is the osmolality of the culture.

20 . The bioreactor system of claim 12 , wherein the probe comprises a Raman analyzer configured with a laser or other suitable light source that operates at wavelengths in a range of 325 nm to 1064 nm.

Assignments (1)

Continuity (4)

References Cited (116)