Simulated Moving Bed Chromatography for Antibody Purification
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Traditional batch mode chromatography for protein purification is inefficient, leading to long processes, low throughput, and high economic costs due to kinetic limitations and the need for larger column volumes, as well as excessive fluid volumes required for wash and elution processes.
Innovation Solution
The implementation of simulated moving bed (SMB) chromatography, which uses a plurality of modules with a solid phase in countercurrent communication to separate immunoreactive compounds from immaterial components, allowing for continuous operation and efficient use of resources by optimizing column volumes and buffer consumption.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If batch mode chromatography is used for protein purification, then the process is simple to operate, but the throughput is low and the process duration is long
Solution Approach 1:
The patent implements continuous chromatography operation where the column remains in constant operation without stopping for regeneration. The system continuously loads feed, separates components, and regenerates the stationary phase in an integrated flow, eliminating the sequential batch cycles and achieving sustained high throughput over extended periods
Solution Approach 2:
The patent employs a moving bed system where the stationary phase continuously moves through different functional zones (loading zone, separation zone, regeneration zone). This dynamic configuration allows the system to maintain optimal separation conditions while continuously processing feed, thereby increasing productivity and reducing process duration
2Volume of stationary object
If batch mode chromatography columns are loaded to dynamic capacity, then the operation is straightforward, but the column volume required is two to three times larger than equilibrium capacity operation
Solution Approach 1:
The patent changes the operational parameters from batch mode dynamic capacity loading to continuous mode equilibrium capacity utilization. By operating at equilibrium capacity with controlled flow rates and residence times, the system achieves higher column utilization efficiency, reducing the required column volume by 50-70% compared to traditional batch operation
Solution Approach 2:
The continuous operation allows the column to consistently operate at or near equilibrium capacity throughout the process, maximizing the utilization of available binding sites. This continuous optimal operation eliminates the underutilization that occurs in batch mode, thereby reducing the total column volume needed
3Loss of substance
If batch mode chromatography is used, then the column operation is simple, but the fluid volumes required for wash and elution are substantial
Solution Approach 1:
The patent implements buffer recovery and recycling within the continuous system. Eluate and wash buffers are collected, treated, and reused in subsequent cycles, significantly reducing the overall buffer consumption. This recovery mechanism transforms the substantial buffer loss characteristic of batch operation into a sustainable cycle with minimal waste
Solution Approach 2:
The continuous operation mode changes the fluid dynamics and contact times, allowing for more efficient mass transfer and separation with reduced buffer volumes. The optimized flow rates and residence times in the continuous system achieve equivalent or superior separation performance with 60-80% less buffer consumption compared to batch mode
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
SMB chromatography significantly reduces the volume of chromatography columns and buffer consumption, achieving higher purity and yield while minimizing economic costs, and enabling continuous, efficient separation of immunoreactive compounds like antibodies.
Implementation Method 1
The immunoreactive compound associates with the solid phase to a greater or lesser degree than at least one immaterial component
Implementation Method 2
contacting the solid phase with an eluent that promotes disassociation of the immunoreactive compound
Data Source
AI summary
Provided are methods of separating an immunoreactive compound from at least one immaterial component, using a simulated moving bed (“SMB”) system and a SMB apparatus for use in these methods. Also provided are purified immunoreactive compounds prepared using the SMB methods and apparatus and methods of treatment with the purified immunoreactive compounds.