Continuous Chromatography Segmentation for High Velocity Binding
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current chromatography methods face challenges in achieving high binding capacities and operational efficiency, particularly in biopharmaceutical purification, where high flow rates reduce binding capacity and increase processing time, limiting productivity.
Innovation Solution
A continuous chromatography method using multiple separation units with specific particle and pore size ranges (30-200 μm and 40-300 nm) and affinity or ion exchange ligands, allowing for continuous flow at velocities above 800 cm/h, enabling high binding capacity utilization and reduced processing time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If high flow rates are used in chromatography, then operational velocity and throughput are improved, but binding capacity is reduced and processing time increases
Solution Approach 1:
The chromatography system is divided into multiple separation units (columns) connected in series, allowing the process to be segmented into multiple binding stages. This enables high flow rates to be maintained while providing sufficient residence time for target molecules to bind to the chromatography matrix through multiple sequential interactions.
Solution Approach 2:
The system operates continuously with feed solution flowing through multiple separation units in sequence, eliminating idle time between batch operations. The continuous flow maintains high operational velocity while the series configuration ensures that target molecules have adequate contact time with the chromatography matrix at each stage, preserving binding capacity.
2Productivity
If high flow rates are used in chromatography, then throughput is improved, but processing time increases
Solution Approach 1:
The processing time is segmented across multiple separation units, where each unit handles a portion of the binding process. This allows the overall throughput to increase with higher flow rates while the residence time in each individual unit remains sufficient for effective binding, preventing excessive total processing time.
Solution Approach 2:
The system performs preliminary binding actions in parallel across multiple separation units simultaneously. While feed solution flows through one unit, other units are already engaged in binding operations, effectively pre-positioning binding capacity to handle incoming flow without increasing overall processing time.
3Productivity
If residence time is reduced to increase productivity, then operational velocity is improved, but binding capacity is compromised
Solution Approach 1:
The binding process is segmented into multiple sequential stages across several separation units. Each unit provides a shorter residence time that is sufficient for partial binding, and the cumulative effect of multiple stages achieves the required overall binding capacity while maintaining high operational velocity through the system.
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 significantly increases productivity by maintaining high binding capacities at low residence times, achieving twice the productivity of batch processes with reduced processing time and buffer requirements.
Implementation Method 1
affinity chromatography mode... ProtA modified affinity chromatography support materials to bind and separate the target molecule
Implementation Method 2
ion exchange chromatography modes
Implementation Method 3
pore diffusion are two main parameters, which influence the target molecule diffusivity towards the adsorption sites
Data Source
Figure 1
Figure 2a
Figure 2b
AI summary
The present invention is directed to a continuous affinity chromatography method and to an apparatus to be used in such method. The method allows the use of high operational velocity while maintaining high binding capacities.