High-temperature characterization of polymers

• US 6,260,407 B1
• Filed: 04/02/1999
• Issued: 07/17/2001
• Est. Priority Date: 04/03/1998
• Status: Expired due to Term

• Current Assignee: Intermolecular Incorporated
• Original Assignee: Symyx Technologies Incorporated (Dassault Systemes SA)
• Inventors: Lee, Thomas S., Dales, G. Cameron, Carlson, Eric D., Petro, Miroslav, Safir, Adam, Nielsen, Ralph B.
• Primary Examiner(s): Williams, Hezron
• Assistant Examiner(s): WIGGINS, JOHN DAVID
• Application Number:
  US09/285,333
• Time in Patent Office: 837 Days
• Field of Search: 73/615.2, 73/615.5, 73/615.7, 73/233.5, 73/232.5, 73/234.1, 738/631.2, 738/648.3, 73/615.8, 73/615.9, 95/87, 95/89, 95/84, 422/70, 422/89, 210/198.2, 210/656
• US Class Current: 73/61.52
• CPC Class Codes: B01D 15/08 Selective adsorption, e.g. chromatography
• CPC Class Codes: B01D 15/14 relating to the introduction of the feed to the apparatus
• CPC Class Codes: B01D 15/161 Temperature conditioning
• CPC Class Codes: B01D 15/26 characterised by the separation mechanism
• CPC Class Codes: B01D 15/265 Adsorption chromatography
• CPC Class Codes: B01D 15/325 Reversed phase
• CPC Class Codes: B01D 15/34 Size selective separation, e.g. size exclusion chromatography, gel filtration, permeation
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 19/26 Nozzle-type reactors, i.e. the distribution of the initial reactants within the reactor is effected by their introduction or injection through nozzles
• CPC Class Codes: B01J 2219/00274 Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00587 High throughput 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 15/0205 by optical means
• CPC Class Codes: G01N 2015/0288 Sorting the particles
• CPC Class Codes: G01N 2015/0294 Particle shape
• CPC Class Codes: G01N 2030/324 speed, flow rate
• CPC Class Codes: G01N 2030/885 involving polymers
• CPC Class Codes: G01N 30/02 : Column chromatography
• CPC Class Codes: G01N 30/16 : Injection G01N30/24 takes precedence
• 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 30/54 : Temperature
• CPC Class Codes: G01N 30/6052 : body
• 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; 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
• CPC Class Codes: Y10S 210/13 : Part flow-full flow

Abstract

Rapid characterization and screening of polymer samples to determine average molecular weight, molecular weight distribution and other properties is disclosed. Rapid flow characterization systems and methods, including liquid chromatography and flow-injection analysis systems and methods are preferably employed. High throughput, automated sampling systems and methods, high-temperature characterization systems and methods, and rapid, indirect calibration compositions and methods are also disclosed. In preferred high-temperature embodiments, the polymer sample is maintained at a temperature of not less than about 75° C. during sample preparation, loading into a liquid chromatography or flow-injection analysis system, injection into a mobile phase of a liquid chromatography or flow-injection analysis system, and/or elution from chromatographic column. The described methods, systems, and device have primary applications in combinatorial polymer research and in industrial process control.

Claims

1. A method for characterizing a polymer sample, the method comprising

withdrawing a polymer sample from a sample container into an injection probe of an auto-sampler, the injection probe being heated to maintain the withdrawn sample at a temperature of not less than about 75°

C. while resident in the injection probe, the heated injection probe residing in a first environment maintained at about ambient temperature while withdrawing the polymer sample,

loading at least a portion of the withdrawn sample into an injection port or a loading port of a liquid chromatography system, the injection port or loading port being adaptable for fluid communication with a chromatographic column, the chromatographic column residing in a heated second environment maintained at a temperature of not less than about 75°

C.,

injecting the loaded sample into a mobile phase of the liquid chromatography system,

maintaining the sample at a temperature of not less than about 75°

C. during a period of time including from when the sample is withdrawn from the sample container to when the sample is within the heated second environment,

chromatographically separating the injected sample, and

detecting a property of the sample or of a component thereof.

2. The method of claim 1 further comprising heating the sample container to maintain the polymer sample at a temperature of not less than about 75°

C. while the sample is resident in the container.

3. The method of claim 1 wherein the injection probe is heated to maintain the withdrawn sample at a temperature of not less than about 100°

C. while resident in the injection probe, the heated second environment is maintained at a temperature of not less than about 100°

C., and the sample is maintained at a temperature of not less than about 100°

C. during a period of time including from when the sample is withdrawn from the sample container to when the sample is injected into the portion of the liquid chromatography system residing in the heated second environment.

4. The method of claim 1 wherein the injection probe is heated to maintain the withdrawn sample at a temperature of not less than about 125°

C. while resident in the injection probe, the heated second environment is maintained at a temperature of not less than about 125°

C., and the sample is maintained at a temperature of not less than about 125°

C. during a period of time including from when the sample is withdrawn from the sample container to when the sample is injected into the portion of the liquid chromatography system residing in the heated second environment.

5. The method of claim 1 wherein the injection probe is heated to maintain the withdrawn sample at a temperature of not less than about 150°

C. while resident in the injection probe, the heated second environment is maintained at a temperature of not less than about 150°

C., and the sample is maintained at a temperature of not less than about 150°

C. during a period of time including from when the sample is withdrawn from the sample container to when the sample is injected into the portion of the liquid chromatography system residing in the heated second environment.

6. The method of claim 1 wherein the injection port or loading port resides in the first environment maintained at about ambient temperature, the method further comprising

advancing the injected sample toward the chromatographic column through a transfer line providing fluid communication between the injection port or loading port and the chromatographic column, and

heating the transfer line to maintain the injected sample at a temperature of not less than about 75° C. while resident in the transfer line.

7. The method of claim 1 wherein the injection port or the loading port resides in the heated second environment maintained at a temperature of not less than about 75°

C.

8. The method of claim 1 wherein at least a portion of the polymer sample is loaded into a loading port in fluid communication with the chromatographic column through a transfer line.

13. The method of claims 1 or 9 wherein at least a portion of the polymer sample is loaded into an injection port.

19. The method of claim 1 or 15 wherein the liquid chromatography system is a high performance liquid chromatography system.

37. The methods of claims 1, 9 or 36 further comprising at least a portion of the sample after withdrawing the sample into the injection probe, and prior to loading at least a portion of the sample.

38. The method of claims 1, 9 or 36 wherein the polymer samples are selected from the group consisting of polymer solutions, polymer emulsions and polymer dispersions.

39. The method of claims 1, 9 or 36 wherein the polymer samples are non-biological polymer samples.

40. The method of claims 1, 9 or 36 wherein the polymer sample comprises a copolymer.

41. A method for analyzing a plurality of non-biological polymer samples, the method comprising providing a library comprising four or more spatially separated non-biological polymer samples, and serially characterizing each of the four or more polymer samples according to the methods of claims 1, 9, 15 or 36.

42. The method of claim 41 wherein the library comprises four or more polymerization product mixtures in reaction vessels, and the samples are withdrawn from the reaction vessels into the injection probe.

43. The method of claims 1, 9 or 36 wherein the detected property is selected from the group consisting of emitted light, refracted light, absorbed light and scattered light.

44. The method of claims 1, 9 or 36 further comprising determining a property of interest from the detected property.

45. The method of claim 44 wherein the determined property is selected from the group consisting of weight-average molecular weight, number-average molecular weight, viscosity-average molecular weight, peak molecular weight, polydispersity index and molecular-weight-distribution shape.

46. The method of claim 44 wherein the determined property is selected from the group consisting of composition and conversion.

47. The method of claim 44 wherein the determined property is particle size.

48. The method of claims 1, 9 or 36 wherein the property is detected with a detector selected from the group consisting of a refractive-index detector, an ultraviolet-visual detector, a photodiode array detector, a static-light-scattering detector, a dynamic-light-scattering detector, an evaporative-light-scattering detector and a capillary viscometer detector.

49. The method of claims 1, 9 or 36 wherein the chromatographic column comprises a stationary-phase and the sample components or polymer molecules of the first and second samples are separated from other respective components or polymer molecules thereof by introducing the samples onto the stationary phase and subsequently eluting the samples or components thereof from the stationary phase with an eluant, the method further comprising

controlling the column geometry, stationary-phase, eluant composition, eluant temperature or eluant flow rate such that the sample-throughput is not more than about 10 minutes per sample.

9. A method for characterizing a polymer sample, the method comprising

withdrawing a polymer sample from a sample container into an injection probe of an auto-sampler, the injection probe being heated to maintain the withdrawn sample at a temperature of not less than about 75°

C. while resident in the injection probe, the heated injection probe residing in a first environment maintained at about ambient temperature,

loading at least a portion of the withdrawn sample into an injection port or a loading port of a flow-injection analysis system, the injection port being adaptable for fluid communication with a continuous-flow detector,

injecting the loaded sample into a mobile phase of the flow-injection analysis system,

detecting a property of the sample or of a component thereof, and

maintaining the sample at a temperature of not less than about 75°

C. during a period of time including from when the sample is withdrawn from the sample container to when the property of the sample or of a component thereof is detected.

10. The method of claim 9 wherein the injection probe is heated to maintain the withdrawn sample at a temperature of not less than about 100°

C. while resident in the injection probe, and the sample is maintained at a temperature of not less than about 100°

C. during a period of time including from when the sample is withdrawn from the sample container to when the property of the sample or of a component thereof is detected.

11. The method of claim 9 wherein the injection probe is heated to maintain the withdrawn sample at a temperature of not less than about 125°

C. while resident in the injection probe, and the sample is maintained at a temperature of not less than about 125°

C. during a period of time including from when the sample is withdrawn from the sample container to when the property of the sample or of a component thereof is detected.

12. The method of claim 9 wherein the injection probe is heated to maintain the withdrawn sample at a temperature of not less than about 150°

C. while resident in the injection probe, and the sample is maintained at a temperature of not less than about 150°

C. during a period of time including from when the sample is withdrawn from the sample container to when the property of the sample or of a component thereof is detected.

14. The method of claim 9 wherein at least a portion of the polymer sample is loaded into a loading port in fluid communication with the continuous-flow detector through a transfer line.

15. A method for characterizing a polymer sample, the method comprising

loading a polymer sample into a liquid chromatography system,

maintaining the loaded polymer sample at a temperature of not less than 75°

C.,

eluting one or more sample components of the polymer sample with a mobile-phase eluant having a temperature of not less than about 75°

C.,

controlling the composition of the mobile-phase eluant to vary over time to separate at least one sample component of the sample from other sample components thereof, and

detecting a property of at least one of the separated sample components.

16. The method of claim 15 wherein the loaded polymer sample is maintained at a temperature of not less than 100°

C. and the mobile-phase eluant has a temperature of not less than about 100°

C.

17. The method of claim 15 wherein the loaded polymer sample is maintained at a temperature of not less than 125°

C. and the mobile-phase eluant has a temperature of not less than about 125°

C.

18. The method of claim 15 wherein the loaded polymer sample is maintained at a temperature of not less than 150°

C. and the mobile-phase eluant has a temperature of not less than about 150°

C.

20. An apparatus for automated sampling of polymer samples for characterization, the apparatus comprising

an injection probe having a surface defining a sample-cavity and an inlet port for fluid communication between the sample cavity and a polymer sample, the probe being adapted for fluid communication with an injection port or a loading port of a continuous-flow polymer characterization system,

a microprocessor for controlling three-dimensional motion of the injection probe between various spatial addresses,

a pump for withdrawing a polymer sample into the injection probe, and

a temperature-control element in thermal communication with the injection probe for maintaining a polymer sample residing in the probe at a predetermined temperature or within a predetermined range of temperatures.

21. The apparatus of claim 20 wherein the temperature-control element is a heating element for maintaining a sample residing in the probe at a temperature of not less than about 75°

C.

22. The apparatus of claim 20 wherein the temperature-control element is a heating element for maintaining a sample residing in the probe at a temperature of not less than about 100°

C.

23. The apparatus of claim 20 wherein the temperature-control element is a heating element for maintaining a sample residing in the probe at a temperature of not less than about 125°

C.

24. The apparatus of claim 20 wherein the temperature-control element is a heating element for maintaining a sample residing in the probe at a temperature of not less than about 150°

C.

25. The apparatus of claim 20 wherein the temperature-control element is a cooling element.

26. The apparatus of claim 20 wherein the probe further comprises a solvent port for fluid communication between a solvent supply line and the sample cavity.

27. The apparatus of claim 20 wherein the continuous-flow polymer characterization system is a high performance liquid chromatography system.

28. The apparatus of claim 20 wherein the continuous-flow polymer characterization system is a flow injection analysis system.

29. The apparatus of claim 20 wherein the temperature control element is a resistive-heating element in adjacent proximity to the sample cavity of the probe.

30. The apparatus of claim 20 wherein the temperature control element is a fluid-type heat exchanger heating element in adjacent proximity to the sample cavity of the probe.

31. The apparatus of claim 20 further comprising a thermocouple for temperature monitoring or control.

32. A high performance liquid chromatography system comprising the automated sampling apparatus of claim 20.

33. A high performance liquid chromatography system comprising

the automated sampling apparatus of claim 20 residing in a first environment,

an enclosure defining a second heated environment, the second heated environment being maintained at a temperature of not less than about 75°

C.,

a chromatographic column residing in the second heated environment,

an injection port or a loading port adaptable for fluid communication with the chromatographic column for injecting polymer samples into the mobile phase,

a reservoir in fluid communication with the chromatographic column for providing a mobile phase thereto and adaptable for fluid communication with the injection port, and

a detector in fluid communication with the chromatographic column for detecting a property of at least one of the sample components.

34. The high performance liquid chromatography system of claim 33 wherein

the automated sampling apparatus resides in the first environment maintained at about ambient temperature, and

the injection port or loading port reside in the second heated environment.

35. A flow-injection analysis system comprising the automated sampling apparatus of claim 20.

36. A method for characterizing a polymer sample, the method comprising

withdrawing a polymer sample from a sample container into an injection probe of an autosampler, the injection probe being heated to maintain the withdrawn sample at a temperature of not less than about 100°

C. while resident in the injection probe, the heated injection probe residing at a first spatial address in a first environment while withdrawing the polymer sample, the first environment being external to a second heated environment,

moving the probe from the first spatial address to a second spatial address,

loading at least a portion of the withdrawn sample into an injection port or a loading port of a high performance liquid chromatography system while the probe is at the second spatial address, the injection port or loading port being internal to the second heated environment and being adaptable for fluid communication with a chromatographic column, the chromatographic column being internal to the second heated environment, the second heated environment being maintained at a temperature of not less than about 100°

C.,

injecting the loaded sample into a mobile phase of the liquid chromatography system,

maintaining the sample at a temperature of not less than about 100°

C. during a period of time including from when the sample is withdrawn from the sample container to when the sample is loaded into the injection port or loading port,

chromatographically separating the injected sample, and

detecting a property of the sample or of a component thereof.