Twin-Column Chromatography for Throughput and Capacity Utilization
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Capture chromatography in biopharmaceutical production faces inefficiencies due to high manufacturing costs of affinity ligands and suboptimal utilization of stationary phase capacity in single column processes, leading to reduced throughput and product losses.
Innovation Solution
A twin-column sequential loading chromatography process with a dual loading flow strategy and process control using a single detector, optimizing flow rates and phases to maximize capacity utilization and throughput, while reducing hardware requirements.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If single column chromatography is used with high linear flow rate to maintain high throughput, then productivity increases, but stationary phase capacity utilization decreases leading to early product breakthrough
Solution Approach 1:
The single chromatography column is divided into multiple segments (first column and second column) that operate in sequence. The first column handles initial loading at high flow rates for throughput, while the second column captures breakthrough material, enabling both high productivity and full capacity utilization across the segmented system.
2Quantity of substance
If single column chromatography is used with low linear flow rate to increase capacity utilization, then stationary phase capacity utilization increases, but throughput decreases
Solution Approach 1:
The chromatography process is segmented into multiple columns operating in sequence, allowing different flow rate strategies for each segment. This enables the system to achieve both high throughput and full capacity utilization that cannot be achieved with a single column operating at uniform flow rate.
3Quantity of substance
If multiple identical columns are used for sequential loading to increase capacity utilization, then stationary phase capacity utilization increases, but device complexity increases
Solution Approach 1:
The invention extracts and utilizes the breakthrough material that would otherwise be lost from the first column by directing it to the second column. This approach maximizes capacity utilization without requiring complex multi-column configurations, as the second column specifically targets the breakthrough fraction rather than requiring parallel operation of multiple full columns.
4Reliability
If column cleaning is performed frequently to maintain product quality, then product purity is maintained, but stationary phase degradation increases reducing column lifespan
Solution Approach 1:
The second column acts as a backup or copy of the first column's function, capturing breakthrough material so that the first column can be more thoroughly cleaned and regenerated without risking product quality. This copying approach allows more aggressive cleaning protocols that extend overall system lifespan while maintaining product purity.
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
The method achieves high productivity and capacity utilization with reduced hardware needs, enabling efficient product recovery and extended stationary phase lifespan, thus lowering production costs.
Implementation Method 1
affinity chromatography stationary phases are used. Affinity materials offer a very high selectivity for the target molecules as they are based on immobilized ligands that bind specifically to the target molecules while letting impurities pass by unaffected
Implementation Method 2
the product concentration can be determined online at that outlet, typically by measuring UV light absorbance
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The invention relates to a chromatographic purification method for the isolation of a desired product fraction from a mixture using 2 chromatographic columns, it relates to methods for setting up such a process, and it also relates to control and/or monitoring and/or optimization processes in this context. The method comprises, within one cycle to be carried out at least once, the following steps: a first batch step (Bl), wherein during a batch timespan said columns are disconnected and a first column (1) is loaded with feed via its inlet using a first flow rate and its outlet is directed to waste, and from a second column (2) desired product is recovered via its outlet and subsequently the second column (2) is regenerated; a first interconnected step (IC1), wherein the outlet of the first column (1) is connected to the inlet of the second column (2) during an interconnected timespan, the first column (1) is loaded beyond its dynamic breakthrough capacity with feed via its inlet using a second flow rate which is the same or larger than the first flow rate, and the outlet of the second column (2) is directed to waste, a second batch step (B2) analogous to the first batch step (Bl) but with exchanged columns; a second interconnected step (IC2), analogous to the first interconnected step (IC1) but with exchanged columns.