Spatial Temperature Gradient Liquid Chromatography

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Solution Overview

Problem

Conventional liquid chromatography faces challenges in achieving focused analyte peaks and high resolution due to band broadening and distortion, often requiring sample concentration and being limited by temperature effects that are less pronounced compared to gas chromatography.

Innovation Solution

Applying a spatially fixed temperature gradient along the length of the chromatography column, with a trap column and separation column each having a temperature gradient, allows for differential analyte-stationary phase affinity, focusing analyte peaks by retaining the head of the peak more strongly than the tail, thereby improving peak resolution and focusing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If a spatial temperature gradient is applied along the chromatography column, then analyte peak focusing and resolution are improved, but device complexity increases due to additional temperature control systems

Engineering Contradiction:
Improveanalyte peak resolutionVSAvoidtemperature control system
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The chromatography column is divided into multiple heating zones along its length, with each zone independently controllable. This segmentation allows creation of a spatial temperature gradient without requiring complete redesign of the entire system, thereby improving resolution while managing complexity through modular temperature control

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Different temperature conditions are applied to different spatial locations along the column. The temperature gradient creates local quality variations where the front and rear portions of analyte bands experience different temperatures, enabling focusing effect that improves peak resolution without uniform system modification

Inventive Principle:
Principle #3Local quality

2Productivity

If the entire column is heated to higher temperatures to reduce mobile phase viscosity, then analysis time is reduced, but analyte retention and separation efficiency deteriorate

Engineering Contradiction:
Improveanalysis timeVSAvoidchromatographic separation efficiency
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The temperature distribution along the column is made dynamic and non-uniform rather than static and uniform. By implementing a spatial temperature gradient, the system achieves optimal balance between mobile phase viscosity reduction (for faster flow) and analyte retention (for separation), allowing high productivity without sacrificing separation efficiency

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The temperature parameter is changed spatially along the column length rather than uniformly. This parameter variation allows different sections of the column to operate at different temperatures, enabling reduced viscosity in certain zones for faster analysis while maintaining higher retention in other zones for efficient separation

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If sample injection volume is increased to analyze dilute samples, then detection sensitivity improves, but peak broadening increases leading to reduced resolution

Engineering Contradiction:
Improvesample concentrationVSAvoidpeak width
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

Temperature is used as a controlling parameter to counteract the broadening effect of large injection volumes. The spatial temperature gradient causes differential migration rates that refocus broadened bands, allowing dilute samples to be analyzed with larger injection volumes without sacrificing peak resolution

Inventive Principle:
Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This method enhances peak resolution and focusing, resulting in narrower and more concentrated elution peaks, improving chromatographic separation efficiency and reducing analysis time, with potential improvements of up to 100% in peak capacity and 50% in signal-to-noise ratio compared to conventional methods.

Implementation Method 1

applying a spatial temperature gradient along at least a portion of the column length... such that a head of a peak corresponding to an analyte among the plurality of analytes is retained more strongly than a tail of the peak under the spatial temperature gradient

Methodology Applied
Scientific EffectTemperature gradient: Temperature Gradient

Implementation Method 2

the plurality of analytes adsorb at the different regions in accordance with their affinities for the stationary phase at the different regions

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentEP3262406B1Spatial temperature gradients in liquid chromatography
Publication Date: 2024.11.13 WATERS TECHNOLOGY CORP
  • EP3262406B1 patent drawingFigure 1A~1D
  • EP3262406B1 patent drawingFigure 2A~2B
  • EP3262406B1 patent drawingFigure 2C

AI summary

Methods for focusing analyte peaks in liquid chromatography using a spatial temperature gradient are provided. Also provided are methods for focusing analyte peaks and improving resolution using a trap column upstream of a separation column. Further, methods are provided in which the trap column placed upstream of the separation column is packed with a temperature- sensitive polymer/copolymer, and a spatial temperature gradient is applied along the trap column for obtaining improved retentivity by trap column stationary phase, and overall improved resolution of analyte peaks.