US 6,730,228 B2Granted

Methods and apparatus for characterization of polymers using multi-dimensional liquid chromatography with regular 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).

Claims41

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 discrete volumes of the first-dimension mobile phase eluent at regularly recurring time intervals, such that at least a portion of each of the first-dimension separated sample components are sampled;
injecting each of the sampled volumes of the first-dimension mobile phase eluent directly into a second-dimension mobile phase of the second dimension of the multi-dimensional liquid chromatography system;
chromatographically separating at least one subcomponent of the sampled portions of each of the first-dimension separated sample components from other subcomponents thereof in a second-dimension liquid chromatography column, such that a second-dimension mobile phase eluent from the second-dimension column comprises two or more second-dimension separated subcomponents for each of the sampled portions of each of the first-dimension separated sample components;
and
detecting a property of the second-dimension separated subcomponents in the second-dimension mobile phase eluent using a flow-through detector.

4 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 discrete volumes of the first-dimension mobile phase eluent at regularly recurring time intervals, such that at least a portion of each of the first-dimension separated sample components are sampled;
injecting each of the sampled volumes of the first-dimension mobile phase eluent directly into a second-dimension mobile phase of the second dimension of the multi-dimensional liquid 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;
chromatographically separating at least one subcomponent of the sampled portions of each of the first-dimension separated sample components from other subcomponents thereof in a second-dimension liquid chromatography column, such that a second-dimension mobile phase eluent from the second-dimension column comprises two or more second-dimension separated subcomponents for each of the sampled portions of each of the first-dimension separated sample components;
and
detecting a property of the second-dimension separated subcomponents in the second-dimension mobile phase eluent using a flow-through detector.

4 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 discrete volumes of the first-dimension mobile phase eluent at regularly recurring time intervals, such that at least a portion of each of the first-dimension separated sample components are sampled;
injecting each of the sampled volumes of the first-dimension mobile phase eluent directly into a second-dimension mobile phase of the second dimension of the multi-dimensional liquid chromatography system;
chromatographically separating at least one subcomponent of the sampled portions of each of the first-dimension separated sample components from other subcomponents thereof in a second-dimension liquid chromatography column, such that a second-dimension mobile phase eluent from the second-dimension column comprises two or more second-dimension separated subcomponents for each of the sampled portions of each of the first-dimension separated sample components;
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.

5 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/230,863Filed 28 Aug 2002 · us provisional application
Priority: 28 Aug 2001
Published: US 2003/0080062 A11 May 2003
Granted: 4 May 2004
Term ends: Not estimatedThe source records don’t support an estimate.

Classification35 codes

G01N 30/463
With serial coupling of separation columns: for multidimensional chromatography
B01D 15/1878
Placed in series: for multi-dimensional chromatography
B01D 15/265
Characterised by the separation mechanism: adsorption chromatography
B01D 15/34
Characterised by the separation mechanism: size-selective separation, e.g. size-exclusion chromatography; Gel filtration; Permeation