Gradient-Elution Multi-Column Separation for Productivity

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Solution Overview

Problem

Current chromatography methods, such as batch chromatography, are inefficient and require complex devices, limiting productivity and purity in separating mixtures, especially when dealing with multiple compounds.

Innovation Solution

A gradient-elution multi-column separation method using at least two chromatography columns mounted in series, where a mixture is discontinuously injected and the enriched fraction is drawn off at a single point, with eluents of varying eluting power injected and displaced periodically to create a composition gradient within the columns.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If batch chromatography with a single column is used, then the method is simple to apply, but productivity is low and products are highly diluted

Engineering Contradiction:
Improvesimplicity of methodVSAvoidproductivity
Core Design Contradiction:
Ease of operationVSProductivity

Solution Approach 1:

The single chromatography column is divided into multiple columns (at least two) connected in series. Each column can be independently eluted with different eluents, allowing parallel processing and increased productivity while maintaining operational simplicity through standardized column modules.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system uses periodic displacement of eluent injection points across multiple columns. By cyclically shifting which eluent is injected into which column, the system achieves continuous productive operation while maintaining simple periodic control patterns that are easy to implement.

Inventive Principle:
Principle #19Periodic action

2Ease of operation

If isocratic elution is used, then the operation is simple, but separation efficiency is limited

Engineering Contradiction:
Improveoperational simplicityVSAvoidseparation efficiency
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The system changes elution parameters by using different eluents with varying eluting powers in different columns. Instead of complex gradient elution in a single column, the invention achieves improved separation efficiency through parameter variation across multiple parallel columns, maintaining operational simplicity.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

Different columns or regions of the multi-column system use different eluents with specific properties optimized for local separation needs. This allows each column to have tailored elution conditions, improving overall separation efficiency while keeping each individual column operationally simple.

Inventive Principle:
Principle #3Local quality

3Productivity

If gradient elution with multiple columns is implemented, then separation efficiency and productivity are enhanced, but device complexity increases

Engineering Contradiction:
ImproveproductivityVSAvoiddevice complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The multiple columns are designed as identical or similar modules that can perform the same chromatography function. This universality reduces device complexity by using standardized components rather than highly specialized different columns, while still achieving enhanced productivity through parallel operation.

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

Solution Approach 2:

The system uses periodic displacement of eluent injection points to simplify control. By cycling through predetermined patterns of eluent injection across columns, the complex gradient elution process is reduced to simple periodic switching, reducing control system complexity while maintaining high productivity.

Inventive Principle:
Principle #19Periodic action

4Device complexity

If batch mode chromatography is used, then the system is simple, but the purified products are highly diluted

Engineering Contradiction:
Improvesystem simplicityVSAvoidproduct concentration
Core Design Contradiction:
Device complexityVSQuantity of substance

Solution Approach 1:

By segmenting the single batch column into multiple series columns, the system can process larger volumes of feed through parallel pathways. This increases the quantity of purified product obtained while maintaining system simplicity through modular column design that can be easily scaled.

Inventive Principle:
Principle #1Segmentation

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 separation efficiency and productivity, allowing for better resolution and reproducibility while simplifying the process, making it suitable for separating synthetic molecules, proteins, and other complex mixtures.

Implementation Method 1

Chromatography is a separation method based on the distribution difference of compounds of a mixture between a mobile phase and a stationary phase, also called an adsorbent phase.

Methodology Applied
Scientific EffectChromatography: Chromatography

Implementation Method 2

Chromatography is a separation method based on the distribution difference of compounds of a mixture between a mobile phase and a stationary phase, also called an adsorbent phase.

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentUS8752417B2Gradient-elution multi-column separation method
Publication Date: 2014.06.17 SARTORIUS CHROMATOGRAPHY EQUIP
  • US8752417B2 patent drawing
  • US8752417B2 patent drawing
  • US8752417B2 patent drawing

AI summary

The invention relates to a method for separating fractions of a mixture to be separated including the steps of providing a device comprising at least two chromatography columns mounted in series, discontinuously injecting a mixture to be separated, in a single point of the device, discontinuously drawing off the fraction enriched in the product of interest, in a single point of the device, and injecting eluents in each column and displacing the points for injection eluents, the eluents having a different eluting power. The method allows efficient separation which is simple to perform.