Continuous Affinity Chromatography for Faster Biomolecule Purification
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Solution Overview
Problem
Existing affinity chromatography methods are inefficient and costly, particularly for large-scale protein purification, due to long cycle times, equipment intensity, and degradation of products, requiring complex setups and high volumes of stationary phases.
Innovation Solution
A continuous multistage process using an elongate body with attached affinity entities, where the liquid flows opposite to the body through conduits, allowing for separate washing and displacement stages to optimize flow rates and conditions, utilizing sonication and agitation for enhanced separation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If batch process affinity chromatography is performed on large scale, then output is improved, but cycle time increases and product degradation occurs
Solution Approach 1:
The patent implements continuous affinity chromatography where the stationary phase is continuously circulated through the mobile phase, eliminating the batch process cycles of loading, washing, and elution. This continuous operation maintains high output while reducing cycle time and preventing product degradation that occurs during batch hold times.
Solution Approach 2:
The patent employs dynamic circulation of the stationary phase through the mobile phase using pumps and conduits, transforming the static batch process into a dynamic continuous system. This allows real-time separation and collection of purified product without the time losses inherent in batch processing.
2Productivity
If large scale affinity chromatography is used, then output is improved, but equipment intensity increases and product degradation occurs
Solution Approach 1:
The patent divides the chromatography system into multiple circulating loops with separate conduits for different stages (loading, washing, elution), allowing each stage to be optimized independently. This segmentation reduces the equipment intensity required for any single stage while maintaining overall high output capability.
Solution Approach 2:
The patent recovers and reuses the mobile phase throughout the continuous circulation process, minimizing waste and reducing the need for large volumes of consumable materials. This recovery approach reduces equipment intensity requirements compared to traditional large-scale batch methods that require extensive fresh material handling.
3Quantity of substance
If fermentation broth is concentrated before affinity chromatography, then flow rate is reduced, but product quality deteriorates and impurities increase
Solution Approach 1:
The patent performs preliminary separation of the stationary phase from the mobile phase before the affinity chromatography process begins, allowing the mobile phase to be pre-treated and optimized. This preliminary action enables direct processing of diluted fermentation broth without requiring concentration steps that would compromise product quality.
4Productivity
If multi-column continuous synthesis is used, then productivity is improved, but device complexity increases due to complex valves and controls
Solution Approach 1:
The patent merges multiple chromatography columns into a single circulating system where the mobile phase flows sequentially through different stages (loading, washing, elution) within one continuous loop. This consolidation achieves multi-column functionality with simplified valve and control requirements, maintaining high productivity while reducing device complexity.
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 enables efficient and cost-effective purification of biomolecules by minimizing product degradation and impurities, allowing for high yields and reduced production costs through optimized flow rates and dedicated apparatus for each stage.
Implementation Method 1
This uses a solid material that has been engineered to adsorb specifically the desired material
Implementation Method 2
attached to the elongate body is an affinity entity, said affinity entity having an affinity for the chemical entity
Implementation Method 3
It may be that the elongate body and/or the liquid is subjected to sonication (e.g. ultrasound) as it passes through the conduit
Implementation Method 4
It may be that the elongate body and/or the liquid is agitated as it passes through the conduit
Data Source
AI summary
This invention relates to a method of removing a chemical entity from a liquid using affinity chromatography. The method involves passing an elongate solid phase through a conduit through which the liquid also flows.