US 6,855,258 B2Granted

Methods for characterization of polymers using multi-dimensional liquid chromatography with parallel second-dimension sampling

AssigneeSymyx Technologies, Inc.

InventorsMiroslav Petro, Son Hoai Nguyen, Eric D. Carlson

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Abstract

Methods and apparatus for characterizing a polymer sample and in preferred embodiments, libraries of polymer samples, in a comprehensive, directly-coupled multi-dimensional liquid chromatography system are disclosed. The first and second dimensions are preferably high-performance liquid chromatography dimensions, such as for example, a first dimension adapted for determining composition (e.g. adapted for mobile-phase gradient elution chromatography, including reverse phase chromatography, adsorption chromatography and the like), and a second dimension adapted for determining molecular weight or particle size (e.g., adapted for size exclusion chromatography, including gel permeation chromatography).

Claims44

Dependent claims

A method for characterizing a polymer sample in a multi-dimensional liquid chromatography system, the method comprising:

injecting the polymer sample into a first-dimension mobile phase of a first dimension of the multi-dimensional liquid chromatography system;
chromatographically separating at least one sample component of the injected polymer sample from other sample components thereof in a first-dimension liquid chromatography column, such that a first-dimension mobile phase eluent from the first-dimension column comprises two or more first-dimension separated sample components;
sampling at least a portion of each of the first-dimension separated sample components from the first-dimension mobile phase eluent for directly-coupled injection through a common injector into a second-dimension of the multi-dimensional chromatography system, the second dimension comprising two or more parallel second-dimension liquid chromatography columns;
continuously supplying a second-dimension mobile phase in parallel through the two or more second-dimension liquid chromatography columns;
serially and distributively injecting the sampled portions of the first-dimension separated sample components directly into the second-dimension mobile phases of the two or more second-dimension liquid chromatography columns, respectively;
chromatographically separating at least one subcomponent of the injected sample portions from other subcomponents thereof substantially simultaneously in the respective second-dimension liquid chromatography columns, such that the two or more second-dimension mobile phase eluents from the associated two or more second-dimension columns each comprise two or more second-dimension separated subcomponents for the sampled portion of the respective first-dimension separated sample component;
and
detecting a property of the second-dimension separated subcomponents in the second-dimension mobile phase eluent using a flow-through detector.

5 more elements

A method for characterizing a polymer sample in a multi-dimensional liquid chromatography system, the method comprising:

injecting the polymer sample into a first-dimension mobile phase of a first dimension of the multi-dimensional liquid chromatography system, wherein the first dimension of the multi-dimensional liquid chromatography system is a high-performance liquid chromatography subsystem adapted for determining compositional variations of first-dimension separated sample components;
chromatographically separating at least one sample component of the injected polymer sample from other sample components thereof in a first-dimension liquid chromatography column, such that a first-dimension mobile phase eluent from the first-dimension column comprises two or more first-dimension separated sample components;
sampling at least a portion of each of the first-dimension separated sample components from the first-dimension mobile phase eluent for directly-coupled injection through a common injector into a second-dimension of the multi-dimensional chromatography system, wherein the second dimension of the multi-dimensional liquid chromatography system is a high-performance liquid chromatography subsystem adapted for size exclusion chromatography comprising two or more parallel second-dimension liquid chromatography columns;
continuously supplying a second-dimension mobile phase in parallel through the two or more second-dimension liquid chromatography columns;
serially and distributively injecting the sampled portions of the first-dimension separated sample components directly into the second-dimension mobile phases of the two or more second-dimension liquid chromatography columns, respectively;
chromatographically separating at least one subcomponent of the injected sample portions from other subcomponents thereof substantially simultaneously in the respective second-dimension liquid chromatography columns, such that the two or more second-dimension mobile phase eluents from the associated two or more second-dimension columns each comprise two or more second-dimension separated subcomponents for the sampled portion of the respective first-dimension separated sample component;
and
detecting a property of the second-dimension separated subcomponents in the second-dimension mobile phase eluent using a flow-through detector.

5 more elements

A method for characterizing a polymer sample in a multi-dimensional liquid chromatography system, the method comprising:

injecting the polymer sample into a first-dimension mobile phase of a first dimension of the multi-dimensional liquid chromatography system, wherein the polymer sample is a member of a library of polymer samples comprising four or more different polymer samples;
chromatographically separating at least one sample component of the injected polymer sample from other sample components thereof in a first-dimension liquid chromatography column, such that a first-dimension mobile phase eluent from the first-dimension column comprises two or more first-dimension separated sample components;
sampling at least a portion of each of the first-dimension separated sample components from the first-dimension mobile phase eluent for directly-coupled injection through a common injector into a second-dimension of the multi-dimensional chromatography system, the second dimension comprising two or more parallel second-dimension liquid chromatography columns;
continuously supplying a second-dimension mobile phase in parallel through the two or more second-dimension liquid chromatography columns;
serially and distributively injecting the sampled portions of the first-dimension separated sample components directly into the second-dimension mobile phases of the two or more second-dimension liquid chromatography columns, respectively;
chromatographically separating at least one subcomponent of the injected sample portions from other subcomponents thereof substantially simultaneously in the respective second-dimension liquid chromatography columns, such that the two or more second-dimension mobile phase eluents from the associated two or more second-dimension columns each comprise two or more second-dimension separated subcomponents for the sampled portion of the respective first-dimension separated sample component;
detecting a property of the second-dimension separated subcomponents in the second-dimension mobile phase eluent using a flow-through detector;
and
repeating the steps of injecting a polymer sample into the first-dimension mobile phase, separating a component of the polymer sample in the first-dimension liquid chromatography column, sampling the first-dimension mobile phase eluent, injecting sampled volumes in to the second-dimension mobile phase, separating a subcomponent of sampled portions of the first-dimension separated components in the second-dimension liquid chromatography column, and detecting a property of the second-dimension separated subcomponents for each of the polymer samples of the library.

6 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/231,316Filed 28 Aug 2002 · continuation in part
Priority: 2 Apr 1999
Published: US 2003/0089663 A115 May 2003
Granted: 15 Feb 2005
Term ends: Not estimatedThe source records don’t support an estimate.

Classification33 codes

G01N 35/1097
For supplying the samples to flow-through analysers: characterised by the valves
B01D 15/1878
Placed in series: for multi-dimensional chromatography
B01D 15/265
Characterised by the separation mechanism: adsorption chromatography
G01N 30/24
Preparation or injection of sample to be analysed: automatic injection systems

Family

Application09/285,363Parent of this continuation-in-part · filed 2 Apr 1999
Application09/285,393Parent of this continuation-in-part · filed 2 Apr 1999
Application09/285,333Parent of this continuation-in-part · filed 2 Apr 1999
Application09/285,335Parent of this continuation-in-part · filed 2 Apr 1999
Application09/285,392Parent of this continuation-in-part · filed 2 Apr 1999
Application09/410,546Parent of this division · filed 1 Oct 1999
Application60/157,338Us provisional application · filed 1 Oct 1999
Application09/670,503Parent of this continuation-in-part · filed 26 Sep 2000
Application60/315,685Us provisional application · filed 28 Aug 2001
Application09/956,199Parent of this continuation-in-part · filed 18 Sep 2001
US 2003/0089663 A1Pre-grant publication · published 15 May 2003
US 6,491,816 B2Parent of this continuation-in-part
US 6,296,771 B1Parent of this division
Application09/956,199Parent of this division
Application09/410,546Parent of this continuation-in-part
US 6,265,226 B1Parent of this continuation-in-part
US 6,260,407 B1Parent of this continuation-in-part
US 6,175,409 B1Parent of this continuation-in-part
US 6,294,388 B1Parent of this continuation-in-part
US 6,436,292 B1Parent of this continuation-in-part
US 2002/0020670 A1Published application
US 6,855,258 B2This patent

From the US filing history. Foreign family members aren’t listed.