Targeted separation protocols for rapid characterizations of polymers

• US 6,491,823 B1
• Filed: 11/28/2000
• Issued: 12/10/2002
• Est. Priority Date: 04/03/1998
• Status: Expired due to Term

• Current Assignee: Intermolecular Incorporated (Merck & Co., Inc.)
• Original Assignee: Symyx Technologies Incorporated (Dassault Systemes SA)
• Inventors: Carlson, Eric, Petro, Miroslav, Safir, Adam, Nielsen, Ralph B.
• Primary Examiner(s): Drodge, Joseph W.
• Application Number:
  US09/728,372
• Time in Patent Office: 742 Days
• Field of Search: 210/198.2, 210/635, 210/656, 210/659, 210/739, 422/70, 436/161, 436/174, 436/180, 73/615.2, 73/615.5, 73/615.6
• US Class Current: 506/7
• 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 15/1871 placed in series
• CPC Class Codes: B01D 15/1885 placed in parallel
• 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 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; Plastics; Rubber; Leather
• 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: Y10T 436/25 : including sample preparation

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. The described methods, systems, and devices have primary applications in combinatorial polymer research and in industrial process control.

Claims

1. A method for targeted screening of a plurality of non-biological polymer samples, the method comprising

serially injecting four or more non-biological polymer samples into a mobile phase of a liquid chromatography system,

determining whether the injected polymer samples comprise a polymer component within a predetermined molecular weight range, by separating at least one sample component of each of the four or more injected polymer samples from other sample components thereof in a column comprising a separation medium effective for targeted chromatographic separation that limits resolution to polymer molecules having molecular weights within the predetermined molecular weight range,

detecting a property of the four or more non-biological polymer samples or of components thereof with a flow-though detector to identify and distinguish between the resolved portions and the unresolved portions of the samples, and

screening at least one component of the resolved portions for a second property of interest with a second characterization system.

2. The method of claim 1 wherein the chromatographic separation medium limits resolution to polymer molecules having a molecular weight ranging from about 10³ to about 10⁴.

3. The method of claim 1 wherein the chromatographic separation medium limits resolution to polymer molecules having a molecular weight ranging from about 10⁴ to about 10⁵.

4. The method of claim 1 wherein the chromatographic separation medium limits resolution to polymer molecules having a molecular weight ranging from ranging from about 10⁵ to about 10⁶.

5. The method of claim 1 wherein the separation medium comprises porous, stationary phase media effective for capturing molecules having a molecular weight up to about 20,000, while passing polymer molecules having a molecular weight larger than about 20,000.

6. The method of claim 1 wherein the separation medium comprises porous, stationary phase media effective for capturing and chromatographically separating polymer molecules having a molecular weight ranging from about 50,000 to about 2,000,000.

7. The method of claim 1 wherein at least one sample component of each of the four or more injected polymer samples is separated from other sample components thereof in a series of two or more chromatographic columns, a first column comprising a separation medium effective for capturing molecules having a molecular weight up to about 20,000, while passing polymer molecules having a molecular weight larger than about 20,000 to a second column, the second column being effective for capturing and chromatographically separating polymer molecules having a molecular weight ranging from about 50,000 to about 2,000,000.

9. The method of claims 1 or 8 wherein the separation medium comprises porous stationary-phase media for size-exclusion chromatography.

10. The method of claims 1 or 8 wherein the chromatographic column has an aspect ratio ranging from about 0.1 to about 1.

11. The apparatus of claims 1 or 8 wherein the chromatographic column has an aspect ratio ranging from about 0.3 to about 1.

12. The apparatus of claims 1 or 8 wherein the chromatographic column has an aspect ratio ranging from about 0.5 to about 1.

13. The method of claims 1 or 8 wherein the average sample throughput for the four or more samples is not more than about 10 minutes per sample.

14. The method of claims 1 or 8 wherein the second characterization system is a second liquid chromatography system and the step of screening a resolved portion comprises screening at least one component of the resolved portion for molecular weight or particle size.

8. A method for targeted screening of a plurality of non-biological polymer samples, the method comprising

serially injecting four or more non-biological polymer samples into a mobile phase of a liquid chromatography system,

determining whether or not the injected polymer samples comprise a polymer component within a predetermined particle size range, by chromatographically separating at least one sample component of each of the four or more injected polymer samples from other sample components thereof in a chromatographic column comprising a separation medium effective for targeted chromatographic separation that limits resolution to polymer molecules having particle sizes within the predetermined particle size range,

detecting a property of the four or more non-biological polymer samples or of components thereof with a flow-through detector to identify and distinguish between the resolved portions and the unresolved portions of the samples, and

screening at least one component of the resolved portions for a second property of interest with a second characterization system.