Continuous Chromatography Control for Real-Time Product Quality
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Solution Overview
Problem
Existing bioprocess purification systems face challenges in accurately determining breakthrough capacities of chromatography columns under varying process conditions, leading to inefficiencies in continuous chromatography operations, particularly due to non-identical columns, unpredictable feed concentration, and flow rate variations, which affect the quality and consistency of the target product over extended durations.
Innovation Solution
A method for controlling a bioprocess purification system using continuous chromatography with at least three columns, employing dynamic control based on UV signal differences and real-time trend analysis to maintain consistent product quality by adjusting upstream and downstream processes, ensuring columns are operated optimally and identifying deviations for real-time corrections.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If breakthrough capacity is determined using traditional fraction collection and high resolution analysis techniques, then measurement precision is improved, but productivity deteriorates due to tedious and laborious work
Solution Approach 1:
The patent replaces manual fraction collection and laboratory analysis (mechanical/chemical processes) with automated UV detection and computer-controlled data processing. The system automatically monitors effluent concentration using UV detectors and calculates breakthrough capacity through software algorithms, eliminating the need for manual fraction collection, HPLC analysis, and biological assays.
Solution Approach 2:
The system performs self-monitoring and self-calculation of breakthrough capacity through automated detection and data processing. The computer automatically analyzes UV detector signals, determines breakthrough points, and calculates capacity values without requiring manual intervention or separate laboratory analysis steps.
2Adaptability or versatility
If feed concentration and process conditions vary with time, then adaptability is improved, but measurement precision deteriorates making true breakthrough capacities impossible to measure accurately
Solution Approach 1:
The system continuously monitors effluent concentration using UV detectors and provides real-time feedback to the control system. This feedback loop allows the system to dynamically adjust measurements and calculations based on actual process conditions, compensating for variations in feed concentration and flow rate to maintain accurate breakthrough capacity determination.
Solution Approach 2:
The patent implements a dynamic measurement system that continuously adapts to changing process conditions. The UV detection system and data processing algorithms operate in real-time, automatically adjusting to variations in feed concentration, flow rate, and other process parameters, enabling accurate breakthrough capacity measurement under dynamic operating conditions.
3Productivity
If continuous chromatography is implemented to improve productivity, then productivity is improved, but device complexity increases due to multiple columns and cyclic operation requirements
Solution Approach 1:
The patent employs multiple identical chromatography columns that can perform different functions at different times in the cycle. Each column can serve as loading column, washing column, or elution column depending on the phase of operation, allowing the system to achieve continuous productivity while using standardized, interchangeable components that simplify overall system design and operation.
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
Enhances the quality and efficiency of bioprocess purification by maintaining consistent product characteristics, optimizing resin utilization, and reducing waste through real-time adjustments, thereby improving the productivity and reliability of continuous chromatography systems.
Implementation Method 1
Often these concentrations are determined by continuously monitoring a signal in a flow through a detector placed in the effluent line
Data Source
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AI summary
The present invention relates to a method for controlling a bioprocess purification system comprising a continuous chromatography configured to operate with at least three columns and configured for cyclic operation, wherein the continuous purification is performed on a sample comprising a target product having desired characteristics. The method comprises detecting (82) at least one parameter indicative of characteristics of the target product, performing (83)real time trend analysis of each detected at least one parameter to identify a deviation from the desired characteristics of the target product, and controlling (84) the bioprocess purification system to meet the desired characteristics based on the identified deviation, whereby the target characteristics is within a pre-determined range.