Enhanced-Fluidity Liquid Mobile Phase for Subcritical Chromatography

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Solution Overview

Problem

Current chromatography processes, particularly in supercritical and subcritical phases, face challenges in achieving efficient separation and enrichment of compounds under restrictive operating conditions, with high pressures and limited scalability for preparative purposes.

Innovation Solution

A chromatographic process using a liquid mobile phase with dissolved gas, where the gas content is between 10 and 50% by volume, operates at a pressure lower than the critical pressure of the gas, allowing for a homogeneous phase at subcritical temperatures and pressures, enabling efficient enrichment in preparative chromatography without the need for high-pressure equipment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If supercritical or subcritical chromatography is used to improve separation efficiency, then separation quality is improved, but operating pressure becomes very high requiring specialized equipment

Engineering Contradiction:
Improveseparation qualityVSAvoidoperating pressure
Core Design Contradiction:
Manufacturing precisionVSStress or pressure

Solution Approach 1:

The invention changes the pressure parameter from supercritical (>73 atm for CO2) to subcritical conditions, and modifies the mobile phase composition by adding significant proportions (10-50%) of low viscosity gases like CO2 to conventional HPLC solvents. This creates an Enhanced-Fluidity Liquid mobile phase that achieves improved separation efficiency without requiring supercritical pressures, thus resolving the contradiction between separation quality and operating pressure.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates a composite mobile phase by combining conventional HPLC solvents (methanol, water, THF) with low viscosity gases (CO2, CHF3). This composite Enhanced-Fluidity Liquid mobile phase combines the solvent power of liquids with the low viscosity and high diffusivity of gases, achieving improved chromatographic separation without the high pressures of supercritical fluids.

Inventive Principle:
Principle #40Composite materials

2Productivity

If EFLC type eluents are used to reduce pressure loss and increase analysis speed, then productivity is improved, but outlet pressure remains very high exceeding pump capabilities

Engineering Contradiction:
Improveanalysis speedVSAvoidoutlet pressure
Core Design Contradiction:
ProductivityVSStress or pressure

Solution Approach 1:

The invention adjusts the operating pressure parameter to be below the critical pressure of CO2 (73 atm), specifically targeting 50-70 atm outlet pressure. This is achieved by optimizing the gas proportion (10-50%) and selecting appropriate solvent combinations, thereby reducing outlet pressure to levels compatible with standard HPLC pumps while maintaining the productivity benefits of enhanced fluidity.

Inventive Principle:
Principle #35Parameter changes

3Manufacturing precision

If high pressure equipment is used to achieve supercritical chromatography, then separation efficiency is improved, but device complexity increases

Engineering Contradiction:
Improveseparation efficiencyVSAvoidequipment requirements
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The invention changes the pressure parameter from supercritical to subcritical range, allowing the use of standard HPLC equipment instead of specialized supercritical fluid chromatography systems. This parameter change maintains separation efficiency benefits while dramatically simplifying equipment requirements and making the technique accessible to routine analytical laboratories.

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 approach reduces operating pressures, increases solvent power, and allows for higher linear speeds and larger injection volumes, enhancing productivity and reducing pressure losses, making it compatible with both HPLC and SFC systems while minimizing equipment requirements.

Implementation Method 1

a liquid mobile phase containing dissolved gas

Methodology Applied
Scientific EffectDissolution: Absorption (physical)

Implementation Method 2

allows for a homogeneous phase at subcritical temperatures and pressures

Methodology Applied
Scientific EffectHomogeneous phase formation:

Implementation Method 3

enabling efficient enrichment in preparative chromatography

Methodology Applied
Scientific EffectChromatography: Chromatography

Data Source

PatentEP2062043B1Method for enriching one or more compounds of a mixture using a liquid mobile phase containing a gas
Publication Date: 2017.11.01 NOVASEP PROCESS SAS
  • EP2062043B1 patent drawingFigure 1
  • EP2062043B1 patent drawingFigure 2
  • EP2062043B1 patent drawingFigure 3

AI summary

The object of the invention is a method for enriching by chromatography of one or more compounds of a mixture in at least one column using an eluent, characterized in that a liquid mobile phase containing dissolved gas is used as eluent. A further object of the invention in the use in preparative chromatography of an eluent composed of a liquid mobile phase containing a dissolved gas.