Fluidized Chromatography Bed Cleaning for Fouled Inlet Regions
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Solution Overview
Problem
Chromatography matrices used in the biopharmaceutical industry face challenges in achieving complete removal of contaminants during cleaning, particularly in the inlet part of the bed, where fouling occurs due to strong adsorption and precipitation, limiting the effectiveness of conventional alkaline cleaning solutions.
Innovation Solution
A process involving the liquefaction of the chromatography bed by raising the movable top adaptor, flowing a cleaning liquid upwards, and repacking the matrix particles to create a consolidated bed, which facilitates the removal of fouling and contaminants by making all bead surfaces accessible for diffusion and hydrodynamic forces.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional alkaline cleaning solutions are used to clean chromatography matrices, then cleaning is performed, but complete removal of contaminants is not achieved, particularly in the inlet part of the bed
Solution Approach 1:
The patent applies dynamics by transforming the static packed bed into a dynamic fluidized bed during the cleaning process. By introducing upward flowing cleaning solution at sufficient velocity, the matrix particles are suspended and fluidized, allowing the cleaning solution to access all bead surfaces including those in the fouled inlet region. This dynamic state enables complete contaminant removal that is unachievable with conventional static cleaning methods.
Solution Approach 2:
The patent changes the flow velocity parameter of the cleaning solution from low (conventional CIP) to high (sufficient to fluidize the bed). This parameter change transforms the cleaning mechanism from surface-level contact to comprehensive bead-suspension cleaning, enabling the cleaning solution to penetrate and remove contaminants from all regions of the bed including the previously inaccessible inlet part.
2Productivity
If high concentration NaOH solutions are used for cleaning, then cleaning efficiency improves, but damage to proteinaceous ligands increases
Solution Approach 1:
The patent implements continuous useful action by maintaining the matrix in a fluidized state throughout the cleaning process. The continuous upward flow of cleaning solution ensures uninterrupted contact with all matrix surfaces, allowing effective cleaning at lower NaOH concentrations. This continuous action eliminates the need for high concentration shocks that would damage proteinaceous ligands, achieving both high cleaning efficiency and ligand preservation.
3Stability of the object's composition
If the bed structure remains consolidated during cleaning, then structural integrity is maintained, but accessibility of cleaning solution to matrix particles is reduced
Solution Approach 1:
The patent applies dynamics by temporarily transforming the consolidated bed structure into a fluidized state during cleaning. The upward flow velocity is increased to suspend the matrix particles, creating a dynamic fluidized bed where cleaning solution can access all surfaces. After cleaning, the flow is reduced and the bed naturally reconsolidates, maintaining structural integrity while achieving complete cleaning accessibility.
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 ensures high matrix purity and sanitization, allowing for the reuse of chromatography matrices with improved separation efficiency and effective cleaning of the entire matrix material, including the fouled top layer, thereby addressing the limitations of conventional cleaning procedures.
Implementation Method 1
making all bead surfaces accessible for diffusion and hydrodynamic forces
Implementation Method 2
making all bead surfaces accessible for diffusion and hydrodynamic forces
Implementation Method 3
The alkali causes desorption of strongly bound contaminants and hydrolyses proteinaceous contaminants
Implementation Method 4
The alkali causes desorption of strongly bound contaminants and hydrolyses proteinaceous contaminants
Data Source
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AI summary
The invention discloses a process for chromatographic separation of at least one target biomolecule from at least one contaminant, comprising the steps of: a) providing an axial chromatography column comprising a consolidated bed of separation matrix particles, where the consolidated bed is confined between a bottom support net and a movable top adaptor; b) separating a target biomolecule from at least one contaminant on the column; c) raising the adaptor by at least 10% of the height of the consolidated bed; d) flowing a cleaning liquid upwards through the bed under conditions sufficient to liquefy the bed, and; e) repacking the matrix particles of the liquefied bed to create a consolidated bed and lowering the adaptor such that it contacts the packed bed and optionally compresses it, and; f) separating a target biomolecule from at least one contaminant on the column.