Expanded Bed Adsorption for Virus-Like Particle Capture

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Solution Overview

Problem

Current methods for purifying recombinant proteins, especially virus-like particles (VLPs), face challenges in efficiently capturing particles of interest from mixtures with high suspended solids content and varying particle sizes, particularly in plant-derived materials, leading to low yields and high costs due to clogging issues and multiple purification steps.

Innovation Solution

The use of Expanded Bed Adsorption (EBA) chromatography with a ligand-based adsorbent bed, allowing for a one-step binding and elution process, where the mixture is loaded onto an expanded bed of adsorbent with a pH between 6.0 and 8.0, enabling efficient capture of VLPs without pre-treatment, scalable for commercial levels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If packed bed adsorption chromatography is used for purification, then purification efficiency is improved, but the process requires removal of whole cells or colloidal debris which is technically challenging and time-consuming

Engineering Contradiction:
Improvepurification efficiencyVSAvoidprocess complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The expanded bed chromatography performs clarification and purification in a single step by allowing the adsorbent to process the feedstock before settling, eliminating the need for preliminary removal of cells or colloidal debris that would be required for packed bed chromatography

Inventive Principle:
Principle #10Preliminary action

2Manufacturing precision

If multiple stages of purification are performed, then purification completeness is improved, but time consumption and sample loss increase

Engineering Contradiction:
Improvepurification completenessVSAvoidpurification time
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The expanded bed chromatography combines clarification and purification into a single integrated process step, merging multiple purification stages that would otherwise be performed separately, thereby reducing time consumption and minimizing sample loss

Inventive Principle:
Principle #5Merging (Combining)

3Manufacturing precision

If packed bed chromatography is used, then purification capability is improved, but resin clogging occurs requiring further clarification by centrifugation or filtration

Engineering Contradiction:
Improvepurification capabilityVSAvoidresin clogging
Core Design Contradiction:
Manufacturing precisionVSObject-generated harmful factors

Solution Approach 1:

The expanded bed configuration performs clarification action before the feedstock reaches the settled bed, preventing resin clogging by allowing cells and colloidal debris to be processed during the expansion phase, eliminating the need for subsequent centrifugation or filtration

Inventive Principle:
Principle #10Preliminary action

4Ease of operation

If expanded bed adsorption is used to reduce clarification demands, then process simplicity is improved, but the method must handle high suspended solids content effectively

Engineering Contradiction:
Improveclarification demandVSAvoidsuspended solids content
Core Design Contradiction:
Ease of operationVSQuantity of substance

Solution Approach 1:

The system dynamically transitions between expanded and settled bed states, allowing the adsorbent to adapt its configuration based on the feedstock characteristics, enabling effective handling of high suspended solids content during expansion while maintaining purification capability in the settled state

Inventive Principle:
Principle #15Dynamics

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 significantly improves the efficiency and yield of capturing VLPs, reducing costs by eliminating the need for multiple purification steps and minimizing clogging issues, while maintaining high purity and scalability for commercial production.

Implementation Method 1

loading the mixture onto the expanded bed of adsorbent to bind the virus like particles

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

It uses the flow of fluid through an initially packed bed structure to achieve contact with a high fluid voidage

Methodology Applied
Scientific EffectFluidization: Fluidisation

Data Source

PatentEP2632562B1Methods for capturing virus like particles from plants using expanded bed chromatography
Publication Date: 2020.08.05 PHILIP MORRIS PRODUCTS SA

AI summary

The present invention relates to a method for capturing virus-like particles of interest from a mixture comprising the use of an expanded bed of adsorbent; suitably wherein said method comprises the steps of: (a) providing an expanded bed of adsorbent; (b) contacting the mixture with the adsorbent such that the constituents of the mixture contact the expanded bed of adsorbent; (c) optionally washing the adsorbent; and (d) optionaliy e!uting the particle of interest from the adsorbent.