Techniques for accelerating thermal equilibrium in a chromatographic column

Patent metadata

Field	Value
Publication number	US-10478750-B2
Application number	US-201314406285-A
Country	US
Kind code	B2
Filing date	Jun 26, 2013
Priority date	Jul 6, 2012
Publication date	Nov 19, 2019
Grant date	Nov 19, 2019

Abstract

Techniques are described for accelerating thermal equilibrium in a chromatographic column. An apparatus comprises a chromatography column, and a plurality of temperature control units in thermal contact with the chromatography column. A method of performing liquid chromatography comprises setting an inlet of a chromatography column to a first temperature using a first temperature control unit in thermal contact with said inlet, setting an outlet of the chromatography column to a second temperature using a second temperature control unit in thermal contact with the outlet, wherein the first temperature is less than the second temperature; and injecting a sample into a liquid stream that flows through the chromatography column after the inlet is set at the first temperature and the outlet is at the second temperature.

First claim

What is claimed is:

1. An apparatus comprising:
at least one memory storing computer-executable code;
a liquid chromatography column having an inner diameter of greater than or equal to about 1.0 mm, the liquid chromatography column comprising an inlet end and an outlet end arranged opposite the inlet end;
a plurality of temperature control units each in thermal contact with a different portion of the liquid chromatography column;
a plurality of thermocouples each for sensing a temperature at a different portion of the liquid chromatography column;
at least one processor operative to execute the computer-executable code to cause the apparatus to:
determine a plurality of temperatures of the liquid chromatography column from the plurality of thermocouples, the plurality of temperatures comprising an inlet temperature T in of the inlet end and an outlet temperature T out of the outlet end, and
individually control at least one of the plurality of temperature control units based on at least one of T in and T out .

2. The apparatus of claim 1 , wherein at least one of the plurality of temperature control units is an outlet temperature control unit in thermal contact with the outlet end, the outlet end being an end of the liquid chromatography column out of which a mobile phase exits the liquid chromatography column.

3. The apparatus of claim 1 , wherein at least one of the plurality of temperature control units is an inlet temperature control unit in thermal contact with the inlet end, the inlet end being an end of the liquid chromatography column into which a mobile phase enters the liquid chromatography column.

4. The apparatus of claim 1 , wherein at least one of the plurality of temperature control units is an inlet temperature control unit used to heat the inlet end to an inlet temperature T in and another of the plurality of temperature control units is an outlet temperature control unit used to heat the outlet end to an outlet temperature T out , the outlet end being located at an end of the liquid chromatography column out of which a mobile phase exits the liquid chromatography column.

5. The apparatus of claim 3 , wherein a first of the plurality of temperature control units is used to cool the inlet of the liquid chromatography column to a first temperature T in and a second of the plurality of temperature control units is used to heat an outlet of the liquid chromatography column to a second temperature T out , the outlet being located at an end of the liquid chromatography column opposite the inlet and being an end out of which the mobile phase exits the liquid chromatography column.

6. The apparatus of claim 1 , wherein an insulating layer surrounds the liquid chromatographic column.

7. The apparatus of claim 6 , wherein the insulating layer is made from any of polystyrene foam, a polymer, polymethacrylate, silicone, urethane, polyolefins, polyamide, polysulfone, polyethyramide, polycarbonate, rubber, polyester, polyfluoroelastomers, polyethylene terephthalate, a ceramic, an aerogel, a fibrous material, methylcellulose and fiberglass.

8. The apparatus of claim 6 , wherein the insulating layer is formed in an area between a jacket surrounding the liquid chromatographic column and the liquid chromatographic column.

9. The apparatus of claim 8 , wherein the insulating layer comprises a vacuum.

10. The apparatus of claim 9 , wherein the vacuum comprises an inert gas.

11. The apparatus of claim 10 , where the inert gas is any of argon, xenon, krypton, carbon dioxide and sulfur hexafluoride.

12. The apparatus of claim 9 , wherein the vacuum comprises atmospheric gas.

13. The apparatus of claim 8 , wherein the insulating layer and the jacket are an integral component of the liquid chromatographic column.

14. The apparatus of claim 6 , wherein the insulating layer comprises a chamber including aerogel particles.

15. The apparatus of claim 1 ,
the plurality of temperature control units comprising an inlet temperature control unit in thermal contact with the inlet end and an outlet temperature control unit in thermal contact with the outlet end.

16. The apparatus of claim 15 , the at least one processor operative to execute the computer-executable code to cause the apparatus to:
control the inlet temperature control unit based on T in , and
control the outlet temperature control unit based on T out .

17. The apparatus of claim 15 , the at least one processor operative to execute the computer-executable code to cause the apparatus to:
receive an inlet temperature setpoint for the inlet end and an outlet temperature setpoint for the outlet end,
control the inlet temperature control unit based on the inlet temperature setpoint and T in , and
control the outlet temperature control unit based on the outlet temperature setpoint and T out .

18. The apparatus of claim 15 , the plurality of temperatures comprising an intermediate temperature T intermediate of an intermediate portion of the liquid chromatography column arranged between the inlet end and the outlet end,
the plurality of temperature control units comprising an intermediate temperature control unit in thermal contact with the intermediate portion.

19. A method of performing liquid chromatography using the apparatus of claim 1 comprising:
setting an inlet of a chromatography column to a first temperature using a first temperature control unit in thermal contact with said inlet;
setting an outlet of the chromatography column to a second temperature using a second temperature control unit in thermal contact with said outlet, wherein the first temperature is less than the second temperature; and
injecting a sample into a liquid stream that flows through the chromatography column after the inlet is set at the first temperature and the outlet is at the second temperature.

20. The method of claim 19 , wherein the chromatography column is thermally insulated.

21. The method of claim 20 , further comprising:
monitoring temperatures at the inlet and the outlet to determine when the inlet is at the first temperature and when the outlet is at the second temperature to thereby determine that the chromatography column is at steady state with respect to column temperature.

22. The method of claim 19 , wherein each of the first temperature control unit and the second temperature control unit performs any of heating and cooling.

23. The method of claim 22 , wherein the first temperature is less than ambient temperature and the second temperature is greater than ambient temperature.

24. The method of claim 22 , wherein the first temperature and the second temperature are greater than ambient temperature.

25. The method of claim 22 , wherein the first temperature and the second temperature are less than ambient temperature.

26. The method of claim 20 , wherein an intermediate point is located on the chromatography column between the inlet and the outlet and the method includes setting the intermediate point of the chromatography column to a third temperature using a third temperature control unit prior to injecting said sample, wherein said third temperature is between said first temperature and said second temperature.

27. The method of claim 26 , wherein said third temperature is determined as a sum of said first temperature and an approximated value, said approximated value being determined as a temperature offs

Assignees

• Waters Technologies Corp

Inventors

• Bouvier Edouard S P
• Kareh Joseph

Classifications

• G01N30/54

  Temperature · CPC title

• B01D15/20

  relating to the conditioning of the sorbent material · CPC title

• B01D15/22

  relating to the construction of the column · CPC title

• G01N2030/3046

  temperature control of column inlet · CPC title

• G01N2030/3076

  using specially adapted T(t) profile · CPC title