Chromatography Device Combining Gel and Membrane Matrices

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Solution Overview

Problem

Current chromatographic separation systems face challenges in achieving high productivity while maintaining dynamic binding capacity, particularly in gel permeation chromatography and membrane adsorption chromatography, due to diffusion limitations and lower capacity at higher flow rates.

Innovation Solution

A device combining a diffusively operable gel chromatography matrix with a downstream convectively operable membrane adsorber, allowing for improved separation performance by enhancing productivity without compromising dynamic binding capacity, characterized by a steep breakthrough curve.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If the linear flow rate is increased to improve productivity, then the throughput increases, but the dynamic binding capacity decreases sharply and breakthrough occurs earlier

Engineering Contradiction:
ImproveproductivityVSAvoiddynamic binding capacity
Core Design Contradiction:
ProductivityVSQuantity of substance

Solution Approach 1:

The chromatography system is divided into multiple stages with different matrices. The first stage uses a gel permeation chromatography matrix for size-based separation at higher flow rates, while the second stage uses an affinity chromatography matrix for specific binding. This segmentation allows each stage to operate in its optimal flow rate range, maintaining high productivity while preserving dynamic binding capacity in the affinity stage.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The gel permeation chromatography matrix acts as an intermediary between the feed stream and the affinity chromatography matrix. It pre-separates the mixture by molecular size, removing larger molecules that would otherwise compete for binding sites in the affinity matrix. This intermediary function protects the affinity matrix from overload and maintains its dynamic binding capacity even at higher overall flow rates.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Speed

If the linear flow rate is increased to reduce processing time, then the processing speed improves, but the separation quality deteriorates due to diffusion limitations

Engineering Contradiction:
Improveprocessing speedVSAvoidseparation quality
Core Design Contradiction:
SpeedVSManufacturing precision

Solution Approach 1:

The separation process is segmented into two distinct mechanisms: size-based separation in the first stage and affinity-based separation in the second stage. The gel permeation stage operates at higher flow rates for rapid size-based fractionation, while the affinity stage operates at lower flow rates to ensure high-quality specific binding. This segmentation allows the system to achieve both high processing speed and high separation quality through different mechanisms.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system changes the separation mechanism parameter between stages. The first stage uses hydrodynamic volume-based separation (gel permeation) which is less sensitive to flow rate changes, allowing higher speeds. The second stage uses affinity-based separation which requires slower flow rates for optimal binding. This parameter change enables the system to maintain separation quality across different flow rate conditions.

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If gel permeation chromatography is used for size-based separation, then the dynamic capacity is high, but the flow rate must be kept relatively low to maintain separation efficiency

Engineering Contradiction:
Improvedynamic capacityVSAvoidflow rate
Core Design Contradiction:
Quantity of substanceVSSpeed

Solution Approach 1:

The system merges gel permeation chromatography and affinity chromatography in series. The gel permeation matrix provides high dynamic capacity for size-based separation at moderate flow rates, while the affinity matrix adds specific binding capability at lower flow rates. The combination allows the system to process larger volumes (high dynamic capacity) while maintaining the flow rates needed for efficient affinity binding.

Inventive Principle:
Principle #5Merging (Combining)

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

The combination of a gel chromatography matrix with a membrane adsorber unit increases productivity by at least 30% while maintaining dynamic binding capacity, effectively separating substances from complex mixtures, such as those found in biological fluids.

Implementation Method 1

Substances of smaller molecular size, or with a smaller hydrodynamic volume, diffuse into the solvent boundary layer or into the pores of the gel and remain there until they diffuse out of the solvent boundary layer or the pores again

Methodology Applied
Scientific EffectDiffusion: Diffusion

Implementation Method 2

In (membrane) adsorption chromatography, components of a fluid, e.g. individual molecules, associates or particles, are bound to the surface of a solid in contact with the fluid

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentEP2389580B1Device and method for material separation
Publication Date: 2017.06.14 SARTORIUS STEDIM BIOTECH GMBH
  • EP2389580B1 patent drawingFigure 1
  • EP2389580B1 patent drawingFigure 2
  • EP2389580B1 patent drawingFigure 3

AI summary

The present invention relates to a device for separating or isolating substances in or from a mixture, wherein the device comprises at least one diffusively operating chromatography matrix and at least one convectively operating chromatography matrix. The present invention further relates to both the use of said device and to a method for separating and/or isolating substances in or from a mixture.