Cyclic Chromatography Adsorber Segmentation for Purity
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Solution Overview
Problem
In flow-through chromatography, there is a trade-off between productivity and product purity due to similar adsorptive properties of the product and impurities, leading to reduced productivity and yield, especially when impurities and products have similar binding characteristics, making it difficult to achieve high purity and high productivity simultaneously.
Innovation Solution
A cyclic chromatographic purification method using a multi-adsorber setup with interconnected adsorber sections, incorporating inline dilution and process control based on detector signals, allows for continuous flow-through chromatography with high productivity and purity by decoupling product recovery and regeneration steps, and utilizing non-affinity chromatography to manage impurities effectively.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If flow-through chromatography is used with similar adsorptive properties of product and impurities, then continuous operation is achieved, but product purity decreases
Solution Approach 1:
The system divides the chromatographic process into multiple adsorber sections (first adsorber section and second adsorber section) that are interconnected. Each section handles specific tasks: the first section retains impurities while allowing product passage, and the second section provides additional purification. This segmentation enables continuous operation while maintaining high product purity through distributed separation functions.
Solution Approach 2:
An inline dilution buffer is introduced as an intermediary substance between the first and second adsorber sections. This buffer dilutes the flow from the first section before it enters the second section, optimizing the conditions for impurity retention while maintaining product passage. The intermediary buffer enables the system to handle similar adsorptive properties of product and impurities effectively.
2Productivity
If loading step is extended to increase productivity, then more product is processed, but impurity breakthrough occurs reducing purity
Solution Approach 1:
The loading function is segmented across two adsorber sections. The first adsorber section is designed to retain impurities during the loading step, while the second adsorber section provides additional retention capacity. This segmentation allows the system to process larger volumes and extend the loading step duration without impurity breakthrough, as the distributed retention capacity prevents saturation at any single point.
Solution Approach 2:
The system performs preliminary impurity retention in the first adsorber section before the flow proceeds to the second section. This preliminary action ensures that impurities are captured early in the process, allowing extended loading without compromising final product purity. The inline dilution buffer further supports this by optimizing retention conditions in the second section.
3Manufacturing precision
If adsorber capacity for impurities is increased, then more impurities are retained, but loading must be stopped sooner reducing productivity
Solution Approach 1:
The impurity retention function is segmented across two adsorber sections. The first adsorber section provides initial impurity retention capacity, and the second adsorber section provides additional retention capacity. This segmentation distributes the retention demand, allowing the system to retain high levels of impurities without stopping loading early, as the total retention capacity is effectively doubled while maintaining continuous operation.
Solution Approach 2:
The interconnected design of the two adsorber sections enables continuous useful action during the loading step. While the first section retains impurities, the second section simultaneously provides additional retention, ensuring continuous impurity removal throughout the loading process. This continuity allows extended loading duration without impurity breakthrough, maintaining both high productivity and high impurity retention.
4Quantity of substance
If bind/elute chromatography is used for product concentration, then product concentration increases, but the process becomes discontinuous
Solution Approach 1:
The system maintains continuous useful action by allowing the product to pass through both adsorber sections during the loading step while impurities are retained. The product stream continues to flow without interruption, enabling continuous operation. Meanwhile, the inline dilution buffer optimizes conditions to ensure product passage while maintaining impurity retention, achieving both concentration and continuity.
Solution Approach 2:
The system inverts the traditional bind/elute approach by allowing the product to flow through (not bind) while impurities are retained. This inversion enables continuous operation because the product stream is not interrupted by binding and elution cycles. The inline dilution buffer supports this inverted approach by optimizing the flow conditions to ensure product passage while maintaining impurity retention, achieving continuous product concentration.
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 continuous flow-through chromatography with enhanced productivity, capacity utilization, and purity, avoiding yield losses by ensuring high product recovery and purity, even when impurities and products have similar adsorptive properties, thus overcoming the trade-off between productivity and purity.
Implementation Method 1
the impurities bind stronger to the chromatographic stationary phase than the product
Data Source
AI summary
A cyclic chromatographic purification method for the isolation of a product from a feed mixture consisting of the product and at least one further component representing impurities, which impurities bind stronger to the chromatographic stationary phase than the product is given. The method uses at least two chromatographic adsorbers as chromatographic stationary phase, grouped into only one first adsorber section (1) and one second adsorber section (2), wherein if an adsorber section comprises more than one chromatographic adsorber these are permanently connected in series, wherein the first adsorber section (1) has a first adsorber section inlet and a first adsorber section outlet, and the second adsorber section (1) has a second adsorber section inlet and a second adsorber section outlet.