Continuous Chromatography Separation Process with Multiple Injections

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Solution Overview

Problem

Existing liquid chromatography methods are complex, require significant equipment and solvent usage, and have limitations in efficiency and scalability due to their discontinuous nature, especially when handling large quantities and multiple injections in a single column.

Innovation Solution

A process involving multiple injections and withdrawals in a chromatography column with controlled time intervals, allowing for the reuse of eluates and fractions, which enables efficient separation and purification without the need for gradient solvents or flow direction changes, and reduces equipment and solvent consumption.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If multiple injections are performed in a single chromatography column, then productivity increases, but the complexity of controlling injection timing and flow management increases

Engineering Contradiction:
ImprovethroughputVSAvoidflow management complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The continuous flow is segmented into discrete injection zones using multiple injection valves positioned at different locations along the column. Each valve operates independently to inject samples at specific positions, allowing multiple injections without interfering with each other's separation process

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system maintains continuous solvent flow through the column at all times, eliminating the need to stop flow between injections. This continuous operation allows multiple samples to be injected and separated simultaneously, maximizing productivity while keeping the system relatively simple

Inventive Principle:
Principle #20Continuity of useful action

2Productivity

If injection frequency is increased, then productivity improves, but separation quality deteriorates due to molecule superposition

Engineering Contradiction:
Improveinjection frequencyVSAvoidseparation quality
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The problem is solved by adding a spatial dimension to the injection process. Instead of injecting multiple samples at the same position sequentially, multiple injection valves are positioned at different locations along the column length. This spatial distribution allows samples to separate in both time and space, preventing superposition and maintaining separation quality even at high injection frequencies

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Quantity of substance

If batch processes or simulated moving bed systems are used, then large quantities can be handled, but device complexity increases due to multiple columns and valve systems

Engineering Contradiction:
Improveprocessing capacityVSAvoidnumber of columns and valves
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

A single chromatography column performs multiple functions simultaneously: it serves as both the separation medium and the pathway for multiple concurrent injections from different positions. The column handles large quantities of material while maintaining simple hardware configuration, eliminating the need for multiple columns and complex valve switching systems required by traditional batch or simulated moving bed approaches

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 process enhances chromatography performance by allowing multiple injections before product elution, tolerates superposition of molecules, and achieves high yields with reduced equipment and solvent use, making it suitable for large-scale applications.

Implementation Method 1

Liquid chromatography is a method of separating the constituents of a mixture. This uses the differences in affinities of the various constituents of the mixture for the same system through which they percolate. This system is composed of a stationary phase and a mobile phase

Methodology Applied
Scientific EffectChromatography: Chromatography

Data Source

PatentEP2637760B1Separation process by means of high flow continuous chromatography, and corresponding device
Publication Date: 2016.02.03 FAUQUET NICOLAS
  • EP2637760B1 patent drawingFigure 1
  • EP2637760B1 patent drawingFigure 2
  • EP2637760B1 patent drawingFigure 3

AI summary

The invention relates to a process for separating fractions of a mixture to be separated by liquid chromatography. According to the invention, such a separation process comprises the steps of: - multiple injections of the mixture to be separated: the injections are carried out successively after time intervals A in a chromatography column, - multiple withdrawals: the withdrawals of fractions from this column are carried out successively after time intervals A, generating an eluate enriched in the fraction of interest, formed from at least one of said withdrawn fractions, - multiple injections of the previously collected eluate: the injections are carried out successively after time intervals B in a second chromatography column, - and multiple withdrawals: the withdrawals of the fractions from this second column are carried out successively after time intervals B. The invention also relates to a device for the implementation of this separation process.