Dry Packing Chromatography Columns via Controlled Swelling

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Solution Overview

Problem

Current liquid chromatography methods for biomolecules face inefficiencies due to suboptimal compression of packed beds in columns, leading to issues like 'tailing' and 'leading' in chromatographic separations, and are not suitable for dry swellable particles, especially for biomolecule separations.

Innovation Solution

A method involving transferring dry swellable particles to a chromatography column, closing it, and then adding liquid to achieve a swollen volume of 105-120% of the column chamber volume, ensuring optimal compression and efficient chromatography, along with precise control of liquid uptake and distribution for high column efficiency and stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Weight of moving object

If dry packing is used for swellable chromatography media, then transport weight is reduced and columns can be delivered dry without preservatives, but the swelling of particles causes poor performance of the packed bed

Engineering Contradiction:
Improvetransport weightVSAvoidpacked bed performance
Core Design Contradiction:
Weight of moving objectVSReliability

Solution Approach 1:

The patent applies preliminary action by pre-calculating the swollen volume of dry particles and determining the exact amount needed to achieve optimal bed compression (105-120% of column volume). This pre-planning allows the bed to be properly compressed after swelling occurs, resolving the performance issue while maintaining the transport weight advantage of dry packing

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent changes the parameter of particle volume by accounting for swelling. Instead of packing based on dry volume, the method calculates the required dry particle amount based on expected swollen volume, ensuring optimal bed compression is achieved after the particles swell in the liquid phase

Inventive Principle:
Principle #35Parameter changes

2Ease of manufacture

If compression of the packed bed is too low, then the bed is easier to pack, but chromatographic separations suffer from tailing and instability

Engineering Contradiction:
Improvepacking easeVSAvoidseparation quality
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The patent uses feedback by monitoring the column volume during packing and adjusting the amount of dry particles added to achieve the target swollen volume of 105-120% of column volume. This feedback mechanism ensures optimal compression is achieved, producing symmetrical peaks and stable separations

Inventive Principle:
Principle #23Feedback

3Stability of the object's composition

If compression of the packed bed is too high, then the bed is more stable, but separations suffer from leading and operating pressures increase

Engineering Contradiction:
Improvebed stabilityVSAvoidoperating pressure
Core Design Contradiction:
Stability of the object's compositionVSStress or pressure

Solution Approach 1:

The patent applies partial or excessive action by intentionally overfilling the column with dry particles to 105-120% of the desired final volume. After the particles swell and compress, this results in optimal bed compression that provides stability without excessive pressure, avoiding the leading effect while maintaining bed integrity

Inventive Principle:
Principle #16Partial or excessive 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 approach results in high column efficiency, low peak asymmetry, and improved long-term stability, enabling effective separation of biomolecules with reduced operating pressures and enhanced throughput.

Implementation Method 1

transferred to a column chamber (2) in a chromatography column (1) an amount of dry swellable particles (5) sufficient to give a swollen volume Vs in a liquid of about 105-120% of the column chamber volume

Methodology Applied
Scientific EffectSwelling: Absorption (physical)

Data Source

PatentUS9958421B2Method for dry packing chromatography columns
Publication Date: 2018.05.01 CYTIVA BIOPROCESS R&D AB
  • US9958421B2 patent drawing
  • US9958421B2 patent drawing
  • US9958421B2 patent drawing

AI summary

The invention provides a packing method for high efficiency chromatography columns starting from dry swellable particles, as well as columns packed by the method and the use of the columns in separation of biomolecules. In the packing method, an amount of dry swellable particles sufficient to give a swollen volume in a liquid of about 105-120% of the column chamber volume is transferred to the column, the column is closed and the liquid is provided to the column.