Flow-Through Chromatography-Diafiltration for Continuous Target Purification
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Solution Overview
Problem
The downstream process of biopharmaceutical production is bottlenecked by the complexity, cost, and time-consuming nature of chromatography unit operations, particularly in separating target components from impurities, which complicates integration into continuous production processes.
Innovation Solution
A separation system integrating a first and second chromatography device with a single-pass crossflow diafiltration unit, allowing for direct combination of flow-through modes with integrated buffer exchange, reducing the process to a single unit operation and minimizing footprints and investment costs while maintaining high yields.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional chromatography unit operations (bind and elute mode) are used for purification, then separation of target component from impurities is achieved, but the process becomes time-consuming and cost-intensive due to multiple buffer systems and操作步骤
Solution Approach 1:
The patent inverts the conventional chromatography approach by using flow-through mode where the target component flows through the column while impurities are retained, rather than the conventional bind-and-elute mode. This inversion eliminates the need for multiple buffer systems and操作步骤, significantly reducing process time while maintaining purification quality
Solution Approach 2:
The patent combines multiple unit operations (chromatography separation and diafiltration) into a single integrated continuous process. The diafiltration unit is directly coupled to the chromatography column, allowing buffer exchange and impurity removal to occur simultaneously with the flow-through separation, thereby reducing overall process time
2Manufacturing precision
If multiple chromatography devices and diafiltration units are used separately, then high purification quality is achieved, but device complexity and footprint increase
Solution Approach 1:
The patent merges the diafiltration unit directly with the chromatography column to create an integrated system. The diafiltration unit is positioned at the outlet of the chromatography column, allowing continuous buffer exchange during the flow-through process. This integration reduces device complexity and footprint while maintaining high purification quality through the combined separation and buffer exchange functions
Solution Approach 2:
The integrated system performs multiple functions simultaneously: the chromatography column separates target component from impurities via flow-through mode, while the diafiltration unit continuously exchanges buffers and removes retained impurities. This multi-functionality reduces the need for separate units and操作步骤, simplifying the overall process
3Ease of operation
If flow-through chromatography mode is used, then operation complexity is reduced and continuous process integration is enabled, but additional diafiltration units are required for buffer exchange between steps
Solution Approach 1:
The patent combines the diafiltration function directly with the chromatography column by positioning the diafiltration unit at the column outlet. This integration allows buffer exchange to occur continuously during the flow-through process without requiring separate diafiltration steps between chromatography operations, thereby maintaining operation simplicity while reducing the total number of unit operations
Solution Approach 2:
The integrated system enables continuous buffer exchange and impurity removal throughout the flow-through chromatography process. The diafiltration unit operates continuously as the feed solution passes through the chromatography column, eliminating the need for discrete buffer exchange steps and maintaining uninterrupted purification action
4Manufacturing precision
If conventional multi-step purification process is used, then impurity removal is effective, but investment costs and footprint increase
Solution Approach 1:
The patent integrates the diafiltration unit with the chromatography column, combining two separate unit operations into a single integrated system. This integration reduces the total number of components required, lowering investment costs and footprint while maintaining effective impurity removal through the combined flow-through separation and continuous buffer exchange functions
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 system achieves high purity and yield in a continuous flow-through operation, reducing complexity and costs by combining three unit operations into one, with efficient impurity removal and target component retention.
Implementation Method 1
the single-pass crossflow diafiltration unit is configured to continuously diafiltrate the second fluid with a diafiltration medium for obtaining a permeate and a third fluid containing the target component as a retentate
Implementation Method 2
the first chromatography device is configured to receive and process the first fluid and to provide a second fluid containing the target component
Implementation Method 3
the second chromatography device is configured to receive and process the third fluid and to provide a fourth fluid containing the target component
Data Source
AI summary
A separation system and methods for separating and purifying a target component include a separation system for separating and purifying a target component, a method for separating and purifying a target component, and the use of a single-pass crossflow diafiltration unit for integrally connecting a first and a second chromatography device.