Method for online sampling an aliquot from a mobile phase comprising an analyte of an apparatus for producing a pharmaceutical or chemical product

Patent metadata

Field	Value
Publication number	US-11313770-B2
Application number	US-201716461891-A
Country	US
Kind code	B2
Filing date	Nov 22, 2017
Priority date	Nov 29, 2016
Publication date	Apr 26, 2022
Grant date	Apr 26, 2022

Abstract

Methods and systems for online sampling an aliquot from a mobile phase comprising an analyte for producing a pharmaceutical or chemical product, wherein the apparatus comprises an analytical device and a tube between an inlet and an outlet, wherein the outlet is in fluid communication with the analytical device, the method comprising: providing a sample device comprising a needle with a needle tip, a septum pierceable by the needle and a pump, wherein the needle is moveable between an extended position in which the septum is pierced by the needle, and a retracted position, in which the septum is not pierced, disposing the sample device at the curved portion of the tube, moving the needle to the extended position such that the needle tip faces the flow direction, and drawing out an aliquot out of the mobile phase.

First claim

The invention claimed is:

1. A method for online analyzing an analyte in both a mobile phase and in an aliquot obtained from the mobile phase, the mobile phase comprising the analyte for producing a pharmaceutical or chemical product, wherein the method comprises:
providing an apparatus comprising an analytical device for detecting the analyte and a tube, wherein the tube comprises an inlet, an outlet and at least one curved portion located between the inlet and the outlet, wherein the outlet is in fluid communication with the analytical device, wherein the mobile phase passes through the tube in a flow direction defined from the inlet to the outlet;
providing a sample device comprising a needle with a needle tip, a septum pierceable by the needle, and a pump, wherein the needle is moveable between an extended position in which the septum is pierced by the needle, and a retracted position in which the septum is not pierced;
disposing the sample device at the curved portion of the tube;
moving the needle to the extended position such that the needle tip faces the flow direction;
operating the pump so as to draw an aliquot out of the mobile phase containing the analyte;
analyzing the analyte in the mobile phase according to at least one analysis method using the analytical device; and
analyzing the analyte in the aliquot drawn out of the mobile phase also using the analytical device.

2. The method according to claim 1 , wherein the curved portion comprises a radial inner wall portion and a radial outer wall portion, wherein the method further comprises disposing the sample device at the radial outer wall portion of the curved portion.

3. The method according to claim 1 , wherein the curved portion is curved such that tube portions of the tube adjacent the curved portion form an angle (α) of 110° to 160° between one another.

4. The method according to claim 1 , further providing the sample device with a check valve.

5. The method according to claim 1 , further comprising orienting the needle tip such that a needle opening disposed at the needle tip is arranged at an angular position relative to a main flow direction defined in a range from a first angular position, in which the needle opening faces a main flow direction of the mobile phase within the curved portion, to a second angular position, in which the needle opening faces away from the main flow direction of the mobile phase within the curved portion.

6. The method according to claim 1 , further comprising operating the pump so as to draw a plurality of discrete aliquots.

7. The method according to claim 1 , further comprising continuously operating the pump so as to continuously draw aliquots out of the mobile phase.

8. The method according to claim 1 , wherein the apparatus comprises a chromatographic column in fluid communication with the inlet, wherein the mobile phase is a pharmaceutical or chemical sample and the chromatographic column prepares the sample.

9. The method according to claim 1 , and further comprising analyzing the analyte of the aliquot drawn out of the mobile phase within the analytical device.

10. The method according to claim 1 , and further comprising associating the results of the analysis of the analyte in the aliquot with the analysis of the analyte in the mobile phase.

11. A system for online analyzing an analyte in both a mobile phase and in an aliquot obtained from the mobile phase, comprising:
an apparatus for producing an analyte for producing a pharmaceutical or chemical product and
a sample device,
wherein the apparatus comprises an analytical device for detecting the analyte and a tube, wherein the tube comprises an inlet, an outlet and at least one curved portion, wherein the outlet is in fluid communication with the analytical device, wherein the curved portion is located between the inlet and the outlet, wherein a flow direction of a mobile phase comprising the analyte is defined from inlet to the outlet,
wherein the sample device comprises a needle with a needle tip, a septum pierceable by the needle and a pump, wherein the needle is moveable between an extended position in which the septum is pierced by the needle, and a retracted position in which the septum is not pierced,
wherein the sample device is disposed at the curved portion of the tube such that the needle tip faces the flow direction in the extended position,
wherein the system is configured to carry out each step of the method according to claim 1 .

12. The system according to claim 11 , wherein the curved portion comprises a radial inner wall portion and a radial outer wall portion, wherein the sample device is disposed at the radial outer wall portion of the curved portion.

13. The system according to claim 11 , wherein the curved portion is curved such that tube portions of the tube adjacent the curved portion form an angle (α) of 110° to 160° between one another.

14. The system according to claim 11 , wherein the needle tip is oriented such that a needle opening disposed at the needle tip is arranged an angular position relative to a main flow direction defined in a range from a first angular position, in which the needle opening faces a main flow direction of the mobile phase within the curved portion, to a second angular position, in which the needle opening faces away from the main flow direction of the mobile phase within the curved portion.

15. The system according to claim 11 , wherein the analytical device is configured to analyze the mobile phase according to at least one analysis method, wherein the system further comprises a further analytical device configured to analyze the analyte of the aliquot drawn out of the mobile phase.

16. The method according to claim 3 , wherein the curved portion is curved such that tube portions of the tube adjacent the curved portion form an angle (α) of 120° to 150°.

17. The method according to claim 3 , wherein the curved portion is curved such that tube portions of the tube adjacent the curved portion form an angle (α) of 125° to 145°.

18. The method according to claim 3 , wherein the curved portion is curved such that tube portions of the tube adjacent the curved portion form an angle (α) of 135°.

19. The system according to claim 13 , wherein the curved portion is curved such that tube portions of the tube adjacent the curved portion form an angle (α) of 120° to 150°.

20. The system according to claim 13 , wherein the curved portion is curved such that tube portions of the tube adjacent the curved portion form an angle (α) of 125° to 145°.

21. The system according to claim 13 , wherein the curved portion is curved such that tube portions of the tube adjacent the curved portion form an angle (α) of 135°.

22. The method of claim 1 in which the needle is parallel to the axis of the inlet of the tube.

23. The method of claim 1 in which the needle is positioned coaxial with the inlet of the tube.

24. A method for analyzing both a mobile phase and an aliquot obtained from the mobile phase, the mobile phase comprising an analyte for producing a pharmaceutical or chemical product, wherein the method comprises:
providing an apparatus comprising an analytical device for detecting the analyte and a tube, wherein the tube comprises an inlet, an outlet and at least one curved portion located between the inlet and the outlet, wherein the outlet is in fluid communication with the analytical device, wherein the mobile phase passes through th

Assignees

• Hoffmann La Roche

Inventors

• Scheidecker Benedikt
• Braaz Reinhard
• Vinnemeier Josef
• Ballin Agathe Justine

Classifications

• G01N1/2035 Primary

  by deviating part of a fluid stream, e.g. by drawing-off or tapping · CPC title

• B01L2300/0832

  cylindrical, tube shaped · CPC title

• B01L2400/0605

  check valves · CPC title

• B01L2300/0672

  Integrated piercing tool · CPC title

• B01L3/0296

  from piercable tubing, e.g. in extracorporeal blood sampling · CPC title