Parallel high-performance liquid chromatography with post-separation treatment

• US 6,436,292 B1
• Filed: 09/26/2000
• Issued: 08/20/2002
• Est. Priority Date: 04/02/1999
• Status: Expired due to Fees

• Current Assignee: Freeslate Inc. (Unchained Labs Inc.)
• Original Assignee: Symyx Technologies Incorporated (Dassault Systemes SA)
• Inventors: Petro, Miroslav
• Primary Examiner(s): Therkorn, Ernest G.
• Application Number:
  US09/670,503
• Time in Patent Office: 693 Days
• Field of Search: 210/635, 210/656, 210/659, 210/143, 210/198.2, 422/70, 436/161, 73/615.2
• US Class Current: 506/6
• CPC Class Codes: B01D 15/1885 placed in parallel
• CPC Class Codes: B01D 15/24 relating to the treatment of the fractions to be distributed
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: C40B 40/14 Libraries containing macromolecular compounds and not covered by groups C40B40/06 - C40B40/12
• CPC Class Codes: G01N 2030/324 speed, flow rate
• CPC Class Codes: G01N 2030/625 by measuring reference material, e.g. carrier without sample
• CPC Class Codes: G01N 2030/628 Multiplexing, i.e. several columns sharing a single detector
• CPC Class Codes: G01N 2030/8429 adding modificating material
• CPC Class Codes: G01N 30/24 Automatic injection systems
• CPC Class Codes: G01N 30/30 of temperature
• CPC Class Codes: G01N 30/461 with serial coupling of separation columns
• CPC Class Codes: G01N 30/466 with separation columns in parallel
• CPC Class Codes: G01N 30/84 Preparation of the fraction to be distributed
• CPC Class Codes: G01N 30/88 Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
• CPC Class Codes: G01N 33/44 Resins; Plastics; Rubber; Leather
• CPC Class Codes: G01N 33/442 Resins; Plastics
• CPC Class Codes: G01N 35/028 having reaction cells in the form of microtitration plates
• CPC Class Codes: G01N 35/085 Flow Injection Analysis
• CPC Class Codes: G01N 35/1097 : characterised by the valves valves in general F16K

Abstract

High-performance liquid chromatography (HPLC) methods and systems are disclosed that combine parallel chromatographic separation of a plurality of samples with a detection technique that involves post-separation treatment of the plurality of samples to enhance one or more properties of the sample or of a component thereof, followed by detection of the one or more enhanced properties. Selective, tunable detection schemes are achievable, and are particularly advantageous as applied in connection with combinatorial chemistry, combinatorial material science and more particularly, combinatorial synthesis and screening of polymeric materials.

Claims

1. A method for characterizing a plurality of polymer samples with a liquid chromatography system, the method comprising

supplying a mobile phase in parallel through each of first and second chromatographic columns of a liquid chromatography system,

injecting first and second polymer samples into the mobile phase of the first and second chromatographic columns, respectively,

separating at least one sample component of the injected first and second samples from other sample components thereof in the respective chromatographic columns, treating the at least one separated sample component of the first and second samples to change a property of at least one separated sample component thereof, and

detecting a property of the treated sample component of the first and second samples.

2. The method of claim 1 wherein the at least one separated sample component of the first and second samples are treated to change an optical property thereof, and the detected property of the treated sample component is an optical property.

3. The method of claim 1 wherein treating comprises precipitating the at least one separated sample component.

4. The method of claim 1 wherein treating comprises selectively precipitating the at least one separated sample component.

5. The method of claim 1 wherein the samples are polymer samples, and treating comprises precipitating the at least one separated sample component by combining the chromatographic eluant with a non-solvent for the at least one separated sample component.

6. The method of claim 1 wherein the samples are polymer samples, and treating comprises precipitating the at least one separated sample component by controlling the temperature of the chromatographic eluant.

7. The method of claim 1 wherein treating comprises derivatizing the at least one separated sample component.

8. The method of claim 1 wherein treating comprises selectively derivatizing the at least one separated sample component.

9. The method of claim 1 wherein at least two or more sample components of the injected first and second samples are separated from each other and from other components thereof.

10. The method of claim 1 wherein the at least one separated sample component of the first and second samples is treated to be selectively detectable over one or more other sample components thereof, and a property of the treated sample is selectively detected thereover.

11. The method of claim 1 wherein ten or more samples are injected into the mobile phase of the first and second chromatographic columns.

12. The method of claim 1 wherein forty or more samples are injected into the mobile phase of the first and second chromatographic columns.

13. The method of claim 1 wherein eighty or more samples are injected into the mobile phase of the first and second chromatographic columns.

14. The method of claim 1 wherein 96*N samples are injected into the mobile phase of the first and second chromatographic columns, where N is an integer ranging from 1 to 5.

15. The method of claim 1 wherein ten or more different samples are injected into the mobile phase of the first and second chromatographic column.

16. The method of claim 1 wherein a property of at least one of the separated sample components of the first and second samples is detected with an optical detector.

17. The method of claim 1 further comprising determining a property of interest.

22. The method of claim 1, 18, 19, 20, or 21 wherein a property of at least one of the separated sample components of the first and second samples is detected in series.

23. The method of claim 1, 18, 19, 20, or 21 wherein a property of at least one of the separated sample components of the first and second samples is detected in parallel.

18. A method for characterizing a plurality of polymer samples with a liquid chromatography system, the method comprising

supplying a mobile phase in parallel through each of first and second chromatographic columns of a liquid chromatography system,

injecting first and second polymer samples into the mobile phase of the first and second chromatographic columns, respectively,

separating at least one sample component of the injected first and second polymer samples from other sample components thereof in the respective chromatographic columns,

precipitating or derivatizing at least one separated sample component of the first and second polymer samples, and

detecting an optical property of a precipitated or derivatized sample component of the first and second polymer samples.

19. A method for characterizing a plurality of polymer samples with a liquid chromatography system, the method comprising

supplying a mobile phase in parallel through each of two or more chromatographic columns of a liquid chromatography system, the mobile phase comprising a solvent for ten or more polymer samples of interest,

injecting the ten or more different polymer samples of interest into the mobile phase of the two or more chromatographic columns,

separating at least one sample component of the injected ten or more polymer samples from other sample components thereof in the respective chromatographic columns,

combining the eluant of the chromatographic column with a non-solvent for the ten or more polymer samples of interest to precipitate the at least one separated sample component thereof, and

detecting an optical property of the precipitated sample component of the ten or more polymer samples.

20. A method for characterizing a plurality of polymer samples with a liquid chromatography system, the method comprising

supplying a mobile phase in parallel through each of first and second chromatographic columns of a liquid chromatography system,

injecting first and second polyer samples into the mobile phase of the first and second chromatographic columns, respectively,

separating at least one sample component of the injected first and second samples from one or more other sample components thereof in the respective chromatographic columns,

controlling the composition or the temperature of the mobile-phase after chromatographic separation, such that an optical property of one or more of the separated sample components of the first and second samples is selectively changed relative to the optical properties of other sample components of the first and second samples, and

selectively detecting the changed optical property of the at least one separated sample component of the first and second samples.

21. A method for characterizing a plurality of samples with a flow-injection analysis system, the method comprising

supplying a mobile phase in parallel through each of first and second flow detectors of a flow-injection analysis system,

injecting first and second polymer samples into the mobile phase of the first and second flow detectors, respectively,

controlling the composition, the flow-rate or the temperature of the mobile-phase after injection of the first and second polymer samples, such that an optical property of one or more of the sample components of the first and second polymer samples is selectively changed relative to the optical properties of other sample components of the first and second polymer samples, and

selectively detecting the changed optical property of the at least one sample component of the first and second polymer samples.