System and method for rapid chromatography with fluid temperature and mobile phase composition control

• US 7,507,337 B2
• Filed: 09/02/2005
• Issued: 03/24/2009
• Est. Priority Date: 09/03/2004
• Status: Expired due to Fees

• Current Assignee: Unchained Labs Inc.
• Original Assignee: Symyx Technologies Incorporated (Dassault Systemes SA)
• Inventors: Song, Li, Hall, Keith Anthony, McWaid, Thomas Harding, Frank, Trevor G., Diamond, Gary M., Petro, Miroslav
• Primary Examiner(s): Therkorn; Ernest G
• Application Number:
  US11/219,073
• Publication Number:
  US 20060054543A1
• Time in Patent Office: 1,299 Days
• Field of Search: 210/635, 210/656, 210/659, 210/101, 210/143, 210/181, 210/198.2
• US Class Current: 210/198.2
• CPC Class Codes: B01D 15/161 Temperature conditioning
• CPC Class Codes: B01D 15/166 Fluid composition conditioning, e.g. gradient
• CPC Class Codes: G01N 30/20 using a sampling valve
• CPC Class Codes: G01N 30/28 Control of physical parameters of the fluid carrier
• CPC Class Codes: G01N 30/30 of temperature
• CPC Class Codes: G01N 30/32 of pressure or speed G01N30/36 takes precedence
• CPC Class Codes: G01N 30/34 of fluid composition, e.g. gradient G01N30/36 takes precedence
• CPC Class Codes: G01N 30/80 Fraction collectors

Abstract

The invention relates to liquid chromatography techniques for rapidly characterizing samples, such as polymer solutions, emulsions and dispersions, and to devices for implementing such techniques. The system includes a design that provides the ability to perform chromatographic separations by using mobile phase composition gradients and temperature gradients during separations. The invention accomplishes this by providing mixing zones for a plurality of fluids as well as heated and chilled feeds feeding the fluids to the mixing zones. Additionally, the system provides the ability to analyze separated components with a detector and/or collect separated fractions into vessels of a fraction collector for further separation and/or analysis.

Claims

1. A liquid chromatography system for characterizing a sample, the system comprising a chromatographic column comprising an inlet port for receiving a mobile phase and the sample, and an effluent port for discharging the mobile phase and separated components of the sample from the chromatographic column, a detector in fluid communication with the effluent port of the chromatographic column for detecting a property of at least one of the sample components, an injection port for injecting the sample into the mobile phase, a fluid distribution system for controlling a composition and a temperature of the mobile phase, the fluid distribution system comprising:

(i) a primary mixing zone adapted to mix a first primary feed and a second primary feed to form the mobile phase, the primary mixing zone being in fluid communication with the inlet port of the chromatographic column, (ii) a first secondary mixing zone adapted to mix a first secondary feed and a second secondary feed to form the first primary feed, the first secondary mixing zone being in fluid communication with the primary mixing zone, and (iii) a second secondary mixing zone adapted to mix a third secondary feed and a fourth secondary feed to form the second primary feed, the second secondary mixing zone being in fluid communication with the primary mixing zone, and a control system for controlling the composition and the temperature of the mobile phase by using one or more control protocols selected from the group consisting of;

(a) varying relative flow rates of the secondary feeds supplied to the first secondary mixing zone, (b) varying relative flow rates of the secondary feeds supplied to the second secondary mixing zone, (c) varying relative flow rates of the first primary feed and the second primary feed supplied to the primary mixing zone, and (d) combinations thereof.

2. The liquid chromatography system of claim 1, further comprising a first line providing fluid communication between the first secondary mixing zone and the primary mixing zone, a first temperature control element in thermal communication with the first line for maintaining the first line at a first temperature, a second line providing fluid communication between the second secondary mixing zone and the primary mixing zone, and a second temperature control element in thermal communication with the second line for maintaining the second line at a second temperature different from the first temperature.

3. The liquid chromatography system of claim 2, wherein the first temperature control element is a resistive-heating element in adjacent proximity to the first line.

4. The liquid chromatography system of claim 2, wherein the second temperature control element is a fluid type heat exchanger, and the second line is located coaxially within an outer tube containing cooling fluid.

5. The liquid chromatography system of claim 1, wherein the system is automated.

6. A liquid chromatography system for characterizing a sample, the system comprising a chromatographic column comprising an inlet port for receiving a mobile phase and the sample, and an effluent port for discharging the mobile phase and separated components of the sample from the chromatographic column, a detector in selective fluid communication with the effluent port of the chromatographic column for detecting a property of at least one of the sample components, a fraction collector in selective fluid communication with the effluent port of the column, an injection port for injecting the sample into the mobile phase, a fluid distribution system for controlling a composition and a temperature of the mobile phase, the fluid distribution system comprising:

(i) a primary mixing zone adapted to mix a first primary feed and a second primary feed to form the mobile phase, the primary mixing zone being in fluid communication with the inlet port of the chromatographic column, (ii) a first secondary mixing zone adapted to mix a first secondary feed and a second secondary feed to form the first primary feed, the first secondary mixing zone being in fluid communication with the primary mixing zone, and (iii) a second secondary mixing zone adapted to mix a third secondary feed and a fourth secondary feed to form the second primary feed, the second secondary mixing zone being in fluid communication with the primary mixing zone, and a control system for controlling the composition and the temperature of the mobile phase by using one or more control protocols selected from the group consisting of;

(a) varying relative flow rates of the secondary feeds supplied to the first secondary mixing zone, (b) varying relative flow rates of the secondary feeds and supplied to the second secondary mixing zone, (c) varying relative flow rates of the first primary feed and the second primary feed supplied to the primary mixing zone, and (d) combinations thereof.

7. The liquid chromatography system of claim 6, further comprising a first line providing fluid communication between the first secondary mixing zone and the primary mixing zone, a first temperature control element in thermal communication with the first line for maintaining the first line at a first temperature, a second line providing fluid communication between the second secondary mixing zone and the primary mixing zone, and a second temperature control element in thermal communication with the second line for maintaining the second line at a second temperature different from the first temperature.

8. The liquid chromatography system of claim 7, wherein the first temperature control element is a resistive-heating element in adjacent proximity to the first line.

9. The liquid chromatography system of claim 7, wherein the second temperature control element is a fluid type heat exchanger, and the second line is located coaxially within an outer tube containing cooling fluid.

10. The liquid chromatography system of claim 6, wherein the system is automated.

11. A liquid chromatography system for characterizing a sample, the system comprising a first chromatographic column comprising an inlet port for receiving a mobile phase and the sample, and an effluent port for discharging the mobile phase and separated components of the sample from the first chromatographic column, a second chromatographic column comprising an inlet port for receiving the mobile phase comprising the sample, and an effluent port for discharging the mobile phase and separated components of the sample from the second chromatographic column, a detector in selective fluid communication with the effluent port of the first and second chromatographic columns for detecting a property of at least one of the sample components, a first injection port for injecting the sample into the mobile, phase, the first injection port in selective fluid communication with the inlet port of the first chromatographic column, a second injection port for injecting the sample into the mobile phase, the second injection port in selective fluid communication with the inlet port of the second chromatographic column, a fluid distribution system for controlling a composition and a temperature of the mobile phase, the fluid distribution system comprising:

(i) a first primary mixing zone adapted to mix a first primary feed and a second primary feed to form the mobile phase, the primary mixing zone being in fluid communication with the inlet port of the first chromatographic column, (ii) a second primary mixing zone adapted to mix the first pry feed and the second primary feed to form the mobile phase, the second primary mixing zone being in fluid communication with the inlet port of the second chromatographic column, (iii) a first secondary mixing zone adapted to mix a first secondary feed and a second secondary feed to form the first primary feed, the first secondary mixing zone being in selective fluid communication with the first and second primary mixing zones, (iii) a second secondary mixing zone adapted to mix a third secondary feed and a fourth secondary feed to form the second primary feed, the second secondary mixing zone being in selective fluid communication with the first and second primary mixing zones, and (iv) a valve located between and in fluid communication with the first and second secondary mixing zones and the first and second primary mixing zones, and being adapted to direct the flow of the first and second primary feeds from the first and second secondary mixing zones to the first primary mixing zone, the second primary mixing zone, or both, and a control system for controlling the composition and the temperature of the mobile phase by using one or more control protocols selected from the group consisting of;

(a) varying relative flow rates of the secondary feeds supplied to the first secondary mixing zone, (b) varying relative flow rates of the secondary feeds supplied to the second secondary mixing zone, (c) varying relative flow rates of the first primary feed and the second primary feed supplied to the first primary mixing zone, (d) varying relative flow rates of the first primary feed and the second primary feed supplied to the second primary mixing zone, and (e) combinations thereof.

12. The liquid chromatography system of claim 11, further comprising a first line providing fluid communication between the valve and the first primary mixing zone, a first temperature control element in thermal communication with the first line for maintaining the first line at a first temperature, a second line providing fluid communication between the valve and the first primary mixing zone, and a second temperature control element in thermal communication with the second line for maintaining the second line at a second temperature different from the first temperature.

13. The liquid chromatography system of claim 12, wherein the first temperature control element is a resistive-heating element in adjacent proximity to the first line.

14. The liquid chromatography system of claim 12, wherein the second temperature control element is a fluid type heat exchanger, and the second line is located coaxially within an outer tube containing cooling fluid.

15. The liquid chromatography system of claim 12, further comprising a third line providing fluid communication between the valve and the second primary mixing zone, a third temperature control element in thermal communication with the third line for maintaining the third line at a third temperature, a fourth line providing fluid communication between the valve and the second primary mixing zone, and a fourth temperature control element in thermal communication with the fourth line for maintaining the fourth line at a fourth temperature different from the third temperature.

16. The liquid chromatography system of claim 15, wherein the third temperature control element is a resistive-heating element in adjacent proximity to the third line.

17. The liquid chromatography system of claim 15, wherein the fourth temperature control element is a fluid type heat exchanger, and the fourth line is located coaxially within an outer tube containing cooling fluid.

18. The liquid chromatography system of claim 15, wherein the first and third temperature are the same temperature.

19. The liquid chromatography system of claim 15, wherein the first temperature is different from the third temperature.

20. The liquid chromatography system of claim 15, wherein the second and fourth temperature are the same temperate.

21. The liquid chromatography system of claim 15, wherein the second temperature is different from the fourth temperature.

22. The liquid chromatography system of claim 12, further comprising a fraction collector in selective fluid communication with the effluent ports of the first and second chromatographic columns.

23. The liquid chromatography system of claim 12, wherein a length of the second chromatographic column is at least one and a half times a length of the first chromatographic column.

24. The liquid chromatography system of claim 12, wherein an inner diameter of the second chromatographic column is at least one and a half times an inner diameter of the first chromatographic column.

25. The liquid chromatography system of claim 12, wherein an internal volume of the second chromatographic column is at least twice an internal volume of the first chromatographic column.

26. The liquid chromatography system of claim 12, wherein the system is automated.

27. A liquid chromatography system for characterizing a sample, the system comprising a chromatographic column comprising an inlet port for receiving a mobile phase and the sample, and an effluent port for discharging the mobile phase and separated components of the sample from the column, a detector in communication with the effluent port of the chromatographic column for detecting a property of at least one of the sample components, an injection valve proximately coupled to the inlet port of the chromatographic column, for injecting the sample with the mobile phase into the chromatographic column, the injection valve comprising:

a primary mixing zone adapted to mix a first primary feed and a second primary feed to form the mobile phase, an injection port adapted for injecting the sample into the injection valve, and an outlet adapted for providing a flow path from the injection valve to the chromatographic column, wherein the outlet of the injection valve and the inlet port of the chromatographic column are proximately coupled, and a control system for controlling the temperature and the composition of the mobile phase by varying relative flow rates of the first primary feed and the second primary feed supplied to the primary mixing zone.

28. A liquid chromatography system for characterizing a sample, the system comprising a chromatographic column comprising an inlet port for receiving a mobile phase comprising the sample, and an effluent port for discharging the mobile phase and separated components of the sample from the column, a detector in selective communication with the effluent port of the chromatographic column for detecting a property of at least one of the sample components, a fraction collector in selective fluid communication with the effluent port of the column, an injection valve proximately coupled to the inlet port of the chromatographic column, for injecting the sample with the mobile phase into the chromatographic column, the injection valve comprising:

a primary mixing zone adapted to mix a first primary feed and a second primary feed to form the mobile phase, an injection port adapted for injecting the sample into the injection valve, and an outlet adapted for providing a flow path from the injection valve to the chromatographic column, wherein the outlet of the injection valve and the inlet port of the chromatographic column are proximately coupled, and a control system for controlling the temperature and the composition of the mobile phase by varying relative flow rates of the fist primary feed and the second primary feed supplied to the primary mixing zone.

29. A liquid chromatography system for characterizing a sample, the system comprising:

a chromatographic column comprising an inlet port for receiving a mobile phase and the sample, and an effluent port for discharging the mobile phase and separated components of the sample from the column, a fraction collector in fluid communication with the effluent port of the chromatographic column for collecting the separated components of the sample in separate vessels, an injection port in selective fluid communication with the inlet port of the chromatographic column for injecting the sample into the mobile phase, a mixing zone adaptable for mixing a first primary feed and a second primary feed to form the mobile phase, and in fluid communication with the inlet port of the chromatographic column, a first line for delivering the first primary feed to the mixing zone, a first temperature control element in thermal communication with the first line for maintaining the first line at a first temperature, a second line for delivering the second primary feed to the mixing zone, a second temperature control element in thermal communication with the second line for maintaining the second line at a second temperature different from the first temperature, and a control system for controlling the composition and the temperature of the mobile phase by using one or more control protocols selected from the group consisting of;

(a) varying relative flow rates of one or more of the feeds, (b) varying the temperatures of the first and second lines, and (c) combinations thereof.

30. A liquid chromatography system for characterizing a sample, the system comprising a chromatographic column located in an ambient temperature environment, the column comprising an inlet port for receiving a mobile phase and the sample, and an effluent port for discharging the mobile phase and separated components of the sample from the chromatographic column, the chromatographic column adapted to be heated or cooled internally by the mobile phase in the absence of any heating chamber, a detector in fluid communication with the effluent port of the chromatographic column for detecting a property of at least one of the sample components, an injection port in selective fluid communication with the inlet port of the chromatographic column for injecting the sample into the mobile phase, a mixing zone adapted to mix a first primary feed and a second primary feed to form the mobile phase, and a control system for controlling a composition and a temperature of the mobile phase by varying the relative flow rates of one or more of the feeds.

31. The liquid chromatography system of claim 30, fiber comprising a first line in fluid communication with the mixing zone, adapted to deliver the first primary feed to the mixing zone, and a first temperature control element in thermal communication with the first line for maintaining the first line at a temperature above 100 degree C.

32. The liquid chromatography system of claim 31, further comprising a second line in fluid communication with the mixing zone, adapted to deliver the second primary feed to the mixing zone, and a second temperature control element in thermal communication with the second line for maintaining the second line at a temperature below 10 degrees C.