Continuous Chromatography With Moving Stationary Phase for Shorter Cycles
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Solution Overview
Problem
Existing chromatography methods, particularly affinity chromatography, face challenges such as high production costs, long cycle times, equipment scale requirements, and product degradation during large-scale processing, leading to increased impurities and lowered yields, especially when dealing with large volumes of liquid from fermentation processes.
Innovation Solution
A method involving the use of an elongate body passed through conduits in a multistage process, where the liquid flows opposite to the body, allowing for various chromatography techniques like affinity, ion exchange, hydrophobic interaction, reverse phase, and hydrophilic interaction chromatography, with stepwise gradients of buffers or solvents to progressively elute components, and the use of sonication and agitation to enhance separation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If batch process affinity chromatography is performed on a large scale, then high outputs are achieved, but long cycle times and extended hold times occur leading to product degradation and increased impurities
Solution Approach 1:
The patent implements continuous chromatography where the stationary phase is continuously moved through the liquid stream, eliminating the batch process cycles of loading, washing, and elution. This continuous operation maintains high productivity while avoiding the extended hold times associated with batch processing, thereby preventing product degradation.
Solution Approach 2:
The invention introduces dynamic movement of the stationary phase through the liquid stream, transitioning from static batch chromatography to dynamic continuous chromatography. The stationary phase is continuously circulated and regenerated, enabling uninterrupted processing that reduces cycle time while maintaining high output.
2Productivity
If large scale chromatography equipment is used, then high outputs are achieved, but hold times are extended causing product degradation
Solution Approach 1:
The continuous circulation and regeneration of the stationary phase eliminates extended hold times. The system continuously processes material without the prolonged stationary phases required in large-scale batch equipment, thereby maintaining high output while preventing product degradation during processing.
3Quantity of substance
If traditional affinity chromatography is used with large volumes of liquid, then purification is achieved, but flow rates for loading stage are much larger than for elution and washing stages
Solution Approach 1:
The continuous movement of the stationary phase through the liquid stream enables uniform flow rates throughout the process. The dynamic circulation system allows the same flow rate to be maintained during loading, washing, and elution stages, eliminating the need for high flow rates only during the loading stage as in traditional batch processes.
4Productivity
If multi-column continuous purification methods are developed, then continuous processing is achieved, but complex valves and controls are required
Solution Approach 1:
The system divides the chromatography process into multiple functional zones along the continuous stationary phase path, with each zone performing a specific function (loading, washing, elution). This segmentation allows continuous processing while using simpler valve and control configurations compared to multi-column systems, as each zone can be independently controlled without requiring complex switching mechanisms.
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 enables efficient, continuous purification with reduced impurities and product degradation, optimizing each stage's flow rates and conditions, thereby improving yield and reducing production costs.
Implementation Method 1
the liquid from which the chemical entity is removed passes along the conduit from the liquid input port to the liquid output port in the opposite direction to the elongate body
Implementation Method 2
This uses a solid material that has been engineered to adsorb specifically the desired material
Implementation Method 3
the use of sonication and agitation to enhance separation
Implementation Method 4
the use of sonication and agitation to enhance separation
Data Source
AI summary
A method of removing a chemical entity from a liquid by passing an elongate body through one or more conduits to remove a chemical entity from a liquid. Each of the one or more conduits includes a liquid input port and a liquid outlet port. The liquid from which the chemical entity is removed passes along the one or more conduits from the liquid input port to the liquid output port in the opposite direction to the elongate body, the one or more conduits being configured such that the liquid contacts the elongate body. The method further includes washing the elongate body to remove products other than the chemical entity.