IP Library › Granted Patent US 11,519,851
Granted Patent B2
US 11,519,851 · App. 16/332,527 · Granted Dec 6, 2022

Monitoring of compounds

Inventors: Craig Harrison (Bridgewater, NJ); Ramsey Shanbaky (Bridgewater, NJ)
Assignee: C Technologies Inc.
G01N21/33B01D15/20B01D35/02B01D65/10G01N21/0303G01N21/05G01N21/272G01N30/50G01N30/74G01N30/88B01D57/02B01D61/20G01N21/0317G01N27/44721G01N30/466G01N2021/1748G01N2030/8886
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Quick Facts
Patent No.
US 11,519,851
App. No.
16/332,527
Granted
Dec 6, 2022
Kind
B2
Abstract

The present invention relates to methods for determining the change in concentration of a substance in solution over time by continuously monitoring in real time. In particular, the present invention relates to methods for continuously monitoring the concentration of compounds during the manufacturing process of biomolecules.

Claims (38)

1. A method of determining the change in concentration of a substance in solution over time comprising:

continuously monitoring in real time the ultraviolet spectrum of the substance by:

measuring the spectrum in a flow through mechanism comprising a light source, a pathlength, a fibrette and a detector, wherein the pathlength is dynamically altered by moving the fibrette to a plurality of dynamically variable pathlengths such that multiple measurements of the spectrum are made at the dynamically variable pathlengths between the fibrette and the detector; wherein the pathlength is dynamically altered in response to real time measurements so that samples are measured without dilution or concentration of the sample;

determining a concentration of the substance based on said measured spectrum;

comparing the concentration of the substance over time; and

generating a control signal in response to the comparison, wherein the control signal adjusts a biotechnology process based on changing process conditions indicated by the comparison.

2. The method of claim 1 wherein the concentration of the substance is monitored at more than one location.

3. The method of claim 2 wherein the substance is a virus particle.

4. The method of claim 1 wherein the substance is a surfactant.

5. The method of claim 1 wherein the substance is a biomolecule.

6. The method of claim 5 wherein the biomolecule is a protein.

7. The method of claim 1 wherein the change in concentration of the substance is due to the solution being subjected to a purification process.

8. The method of claim 7 wherein the purification process is precipitation, filtration, electrophoresis, chromatography separation and combinations thereof.

9. The method of claim 8 wherein the chromatographic separation comprises a step selected from the group consisting of anion exchange chromatography, cation exchange chromatography, gel filtration chromatography, hydrophobic interaction chromatography and affinity chromatography.

10. The method of claim 8 wherein the filtration is ultrafiltration or diafiltration or combinations thereof.

11. The method of claim 1 , wherein the biotechnology process comprises monitoring a chromatography column, and wherein said control signal reroutes a flow of the substance to an alternative chromatography column when the comparison indicates the concentration of the substance is outside a predetermined range.

12. The method of claim 1 , wherein the step of determining the concentration of the substance is performed without knowing the path lengths.

13. A method of determining the change in concentration of a substance in solution over time comprising:

monitoring in real time the ultraviolet spectrum of the substance at discrete time points by:

measuring the spectrum in a flow through mechanism comprising a light source, a pathlength, a fibrette and a detector, wherein the pathlength is dynamically altered by moving the fibrette to a plurality of dynamically variable pathlengths such that multiple measurements of the spectrum are made at the dynamically variable pathlengths between the fibrette and the detector at the discrete time points; wherein the pathlength is dynamically altered in response to real time measurements so that samples are measured without dilution or concentration of the sample;

determining a concentration of the substance based on said measured spectrum;

comparing the concentration of the substance at the discrete time points; and

generating a control signal in response to the comparison, wherein the control signal adjusts a biotechnology process based on changing process conditions indicated by the comparison.

14. The method of claim 13 wherein the concentration of the substance is monitored at more than one location.

15. The method of claim 13 wherein the change in concentration of the substance is due to the solution being subjected to a purification process.

16. The method of claim 15 wherein the purification process is precipitation, filtration, electrophoresis, chromatography separation and combinations thereof.

17. The method of claim 16 wherein the chromatographic separation comprises a step selected from the group consisting of anion exchange chromatography, cation exchange chromatography, gel filtration chromatography, hydrophobic interaction chromatography and affinity chromatography.

18. The method of claim 13 , wherein the biotechnology process comprises monitoring a chromatography column, and wherein said control signal reroutes a flow of the substance to an alternative chromatography column when the comparison indicates the concentration of the substance is outside a predetermined range.

19. The method of claim 13 , wherein the step of determining the concentration of the substance is performed without knowing the path lengths.

20. A method of determining the lifetime of a membrane used in ultrafiltration comprising:

continuously monitoring in real time the concentration of a substance in a solution that has passed through the ultrafiltration membrane by:

measuring the ultraviolet spectrum of the substance in a flow through mechanism comprising a light source, a pathlength, a fibrette and a detector, wherein the pathlength is dynamically altered by moving the fibrette to a plurality of dynamically variable pathlengths such that multiple measurements of the spectrum are made at the dynamically variable pathlengths between the fibrette and the detector; wherein the pathlength is dynamically altered in response to real time measurements so that samples are measured without dilution or concentration of the sample;

determining a concentration of the substance based on said measured spectrum;

comparing the concentration of the substance over time; and

generating a control signal in response to the comparison, wherein the control signal adjusts a biotechnology process based on changing process conditions indicated by the comparison.

21. The method of claim 20 further comprising continuously monitoring in real time the concentration of the substance in the solution prior to the solution passing through the ultrafiltration membrane.

22. The method of claim 20 , wherein the said control signal reroutes a flow of the substance to an alternative ultrafiltration membrane when the comparison indicates the concentration of the substance is outside a predetermined range.

23. The method of claim 20 , wherein the step of determining the concentration of the substance is performed without knowing the path lengths.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 2, 2025
From: C TECHNOLOGIES INC.
To: REPLIGEN CORPORATION
Reel/Frame 071004/0948 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 7, 2021
From: SHANBAKY, RAMSEY; HARRISON, CRAIG
To: C TECHNOLOGIES INC.
Reel/Frame 057362/0451 →
Continuity (2)
Provisional Application 62495653 · Sep 17, 2016
Related Publication 20190212258A1 · Jul 11, 2019