Automated system and method for analyzing samples from a bioreactor

Abstract

This invention provides a method and apparatus for the automated analysis of samples from a bioreactor. [Solution] A sample is drawn from the bioreactor 12 by a pump 16 from a probe 14. The drawn sample is collected in an intermediate vial 22 and then introduced into a first liquid chromatography apparatus 28 to purify the target protein. The sample stream containing the purified target protein is introduced into a second liquid chromatography apparatus 50 for analysis of the target protein. A two-stage liquid chromatography process is provided, using the first liquid chromatography 28 for purification and the second liquid chromatography 50 for analysis.

Claims

1. An automated system for analyzing at least one sample from a bioreactor, A probe for extracting at least one sample from the bioreactor, A pump that applies pressure to the at least one sample drawn out so that it becomes a sample flow, A first conduit connected to the pump to carry the flow of the aforementioned sample, A first liquid chromatography apparatus having a main inlet and a main outlet, wherein the main inlet is connected to a first conduit to receive the sample flow, the first liquid chromatography apparatus is configured to purify at least one target protein in the sample flow to generate a purified sample flow, and the purified sample flow is discharged from the main outlet, A second conduit connected to the main discharge port for carrying the flow of the purified sample, A flow splitter having a splitter inlet, a branch outlet, and a splitter outlet, wherein the splitter inlet is connected to the second conduit to receive the flow of the purified sample, and a flow restrictor is associated with the branch outlet so as to be able to discharge a portion of the flow of the purified sample from the branch outlet as a portion of the flow of the purified sample, and the flow of the purified sample that is not discharged from the branch outlet is discharged from the splitter outlet as an outflow flow, A third conduit connected to the branch outlet to carry a portion of the flow of the purified sample, A second liquid chromatography apparatus having a second inlet connected to a third conduit for receiving a portion of the purified sample, wherein the second liquid chromatography apparatus is configured to analyze at least one target protein in the portion of the purified sample. Equipped with, system.

2. The at least one sample drawn is collected from the bioreactor into one or more intermediate vials. The system according to claim 1.

3. The pump extracts at least one of the extracted samples from the one or more intermediate vials, and then applies pressure to the at least one of the extracted samples so that it becomes a sample flow. The system according to claim 2.

4. The first liquid chromatography apparatus includes one or more main vials for collecting the sample flow. The system according to claim 3.

5. The first liquid chromatography apparatus is a first-dimensional liquid chromatography apparatus. The system according to claim 1.

6. The pump further comprises a filter for filtering the at least one sample before applying pressure. The system according to claim 1.

7. The flow of a portion of the purified sample is less than 50% of the flow of the purified sample. The system according to claim 1.

8. The system further comprises at least one sample collection loop for collecting a portion of the flow of the purified sample to accumulate a predetermined amount for analysis by the second liquid chromatography apparatus. The system according to claim 1.

9. A method for automated analysis of at least one sample from a bioreactor, To extract at least one sample from the bioreactor, Applying pressure to the at least one of the drawn-out samples so that it becomes a sample flow, To generate a purified sample stream, at least one target protein in the sample stream is purified using a first liquid chromatography apparatus. The purified sample flow is separated into a portion of the purified sample flow and an outflow flow, and Using a second liquid chromatography apparatus, analyze the at least one target protein in a portion of the purified sample flow. including, method.

10. The at least one sample drawn is collected from the bioreactor into one or more intermediate vials. The method according to claim 9.

11. The pump draws the at least one sample that has been drawn out from the one or more intermediate vials, and then applies pressure to the at least one sample that has been drawn out so that it becomes a sample flow. The method according to claim 10.

12. The first liquid chromatography apparatus includes one or more main vials for collecting the sample flow. The method according to claim 11.

13. The first liquid chromatography apparatus is a first-dimensional liquid chromatography apparatus. The method according to claim 9.

14. Further including filtering the at least one of the drawn samples before applying pressure, The method according to claim 9.

15. The flow of a portion of the purified sample is less than 50% of the flow of the purified sample. The method according to claim 9.

16. The aforementioned at least one sample comprises one or more monoclonal antibodies. The method according to claim 9.

17. The at least one sample comprises one or more Fc fusion proteins. The method according to claim 9.

18. The further step includes collecting a portion of the purified sample stream to accumulate a predetermined amount before analyzing the at least one target protein in the portion of the purified sample stream using the second liquid chromatography apparatus, The method according to claim 9.

19. A portion of the purified sample is collected in at least one sample collection loop. The method according to claim 18.

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