Chromatography Column Packing Using External Drive Compression

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Solution Overview

Problem

Existing chromatography column packing methods, such as flow packing and axial compression, suffer from axial and radial heterogeneity, leading to poor bed stability and increased mechanical complexity, cost, and require high liquid pressures, making them unsuitable for wide bore columns and disposable columns.

Innovation Solution

A method using an external drive means for axial compression, allowing for homogeneous bed formation and reduced mechanical complexity, compatible with low-pressure fluid handling, and enabling aseptic packing of pre-sterilized columns, which reduces costs and maintains column efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If flow packing method is used to compress the bed, then the bed is compressed to target height, but axial heterogeneity occurs with highest compression at outlet and zero compression at top, leading to bed relaxation and particle re-arrangement

Engineering Contradiction:
Improvebed compression uniformityVSAvoidbed stability
Core Design Contradiction:
Manufacturing precisionVSStability of the object's composition

Solution Approach 1:

The patent inverts the conventional flow packing approach by introducing slurry from the bottom end instead of the top end. This reversal ensures that the slurry is first deposited at the bottom where support is provided by the lower frit, preventing particle re-arrangement and channel formation. The slurry then consolidates upward through the column, achieving uniform compression throughout the bed height while maintaining bed stability.

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The patent applies preliminary action by providing mechanical support from the lower frit before slurry introduction. The lower frit is positioned and secured beforehand to provide immediate support structure. Additionally, the slurry is introduced at controlled flow rates that allow progressive consolidation from bottom to top, preventing premature bed collapse or heterogeneity formation during the packing process.

Inventive Principle:
Principle #10Preliminary action

2Stress or pressure

If axial compression method is used to remove high liquid pressure requirement, then mechanical complexity and cost increase due to motor drives or hydraulic systems attached to column

Engineering Contradiction:
Improveliquid pressure during packingVSAvoidcolumn mechanical complexity
Core Design Contradiction:
Stress or pressureVSDevice complexity

Solution Approach 1:

The patent applies self-service by utilizing the natural properties of the slurry and the column structure itself to achieve compression without external mechanical systems. The slurry's own weight and the flow dynamics during introduction provide the compression force needed. The frits and column housing serve dual purposes as both structural support and compression elements, eliminating the need for separate motor drives or hydraulic systems.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent replaces the mechanical compression systems (motor drives, hydraulic systems) with a fluid-based compression approach. Instead of using mechanical force to compress the bed, the method uses controlled slurry flow and consolidation to achieve compression. The liquid carrier and slurry introduction system substitute for complex mechanical compression apparatus, reducing device complexity while maintaining effective bed compression.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Quantity of substance

If flow packing is used for wide bore columns, then equipment requires high packing pressure substantially higher than operation pressure, but this is undesirable for preparative chromatography

Engineering Contradiction:
Improvecolumn capacityVSAvoidpacking pressure
Core Design Contradiction:
Quantity of substanceVSStress or pressure

Solution Approach 1:

The patent applies parameter changes by modifying the slurry flow rate and composition parameters during the packing process. The slurry is introduced at flow rates and concentrations optimized for wide bore columns, allowing consolidation at pressures comparable to operational pressures. The carrier liquid properties and slurry viscosity are adjusted to facilitate smooth flow and consolidation in large diameter columns without requiring excessive pressure.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses preliminary action by pre-establishing the support structure with the lower frit and planning the slurry introduction strategy before packing wide bore columns. The column geometry and frit positioning are predetermined to accommodate the larger volume and lower pressure requirements. This preliminary preparation allows the use of gentler packing conditions suitable for preparative-scale columns.

Inventive Principle:
Principle #10Preliminary action

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 achieves improved bed stability and column efficiency with reduced mechanical complexity and cost, enabling scalable and aseptic packing of chromatography columns, suitable for both preparative and analytical scales.

Implementation Method 1

compressing the bed of particulate medium to produce the target bed height by axial movement of the first and/or second end filters using said drive means

Methodology Applied
Scientific EffectAxial compression: Compression

Implementation Method 2

introducing a suspension of the particulate medium into the bed space via the first valve means to provide a bed of particulate medium therein

Methodology Applied
Scientific EffectSlurry introduction and consolidation: Sedimentation

Data Source

PatentEP2554229B1Packing system and method for chromatography columns
Publication Date: 2020.11.18 CYTIVA BIOPROCESS R&D AB
  • EP2554229B1 patent drawingFigure 1
  • EP2554229B1 patent drawingFigure 2
  • EP2554229B1 patent drawingFigure 3

AI summary

The invention relates to a system for packing chromatography columns with a chromatography medium and packing method for use in such columns. In particular, the invention relates to a method and system for packing chromatography columns which utilises an external drive means to compress a bed of particulate medium to a target bed height.