Chromatography Column Breakthrough Monitoring and Cycle Adjustment
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Solution Overview
Problem
The existing bioprocess purification systems using small volume columns in capture chromatography are time-consuming and inefficient, requiring modifications to enhance the cyclic purification process while maintaining high yield and efficiently utilizing available chromatography system capacity.
Innovation Solution
Implementing a method that includes continuous cell culture processes, automated decision points, and real-time monitoring using sensors to control the purification process, adjusting parameters like loading time, sample feed volume, and elution based on measured parameters to optimize chromatography performance and extend column lifespan.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If small volume columns are used in capture chromatography, then the chromatography system capacity is efficiently utilized, but the purification process becomes time-consuming
Solution Approach 1:
The cyclic purification process is segmented into distinct phases (loading, washing, eluting, cleaning) that can be optimized independently. The method segments the time-consuming processes to identify and reduce bottlenecks while maintaining efficient column utilization.
Solution Approach 2:
The purification process parameters are made dynamic and adaptive. The method continuously monitors process parameters and adjusts loading rates, wash volumes, and elution conditions in real-time based on actual column performance and product characteristics, optimizing both speed and efficiency.
2Productivity
If the purification process is accelerated to reduce time, then productivity improves, but the yield may be compromised
Solution Approach 1:
The method implements continuous feedback monitoring of process parameters including UV absorbance, pressure, and flow rates throughout the purification cycle. This real-time data feeds back to adjust process conditions, ensuring that acceleration does not compromise binding efficiency or product recovery, thus maintaining high yield while improving productivity.
Solution Approach 2:
The purification process utilizes dynamic parameter changes including pH gradients, ionic strength variations, and temperature adjustments during different phases of the cyclic process. These parameter changes are optimized to maintain product binding and recovery efficiency while reducing overall process time through faster equilibration and elution rates.
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 reduces the time required for product purification, adapts the process to efficiently use chromatography system capacity, and maintains high yield by optimizing chromatography performance and extending column lifespan through real-time monitoring and automation.
Implementation Method 1
the clarified or clear feed from the bioreactor is introduced into a column capture chromatography system configured for a cyclic purifying process to extract the product
Data Source
AI summary
The present invention relates to a method for monitoring operational status in a column capture chromatography system configured for cyclical repetitive purification performed on a volume of sample feed comprising at least one product configured to be captured in the column during loading. The method comprises: performing (51) a purification cycle; measuring (52) at least one parameter during the purification cycle indicative of breakthrough of the at least one captured product after the column during loading of sample feed; when breakthrough is detected, reducing (56a) the amount of sample feed loaded during loading in the next purification cycle; and repeating the steps to perform another purification cycle. Each purification cycle comprising: loading an amount of sample feed onto the column, washing the column and eluting the at least one product.