Chromatography Flow Routing for Multi-Attribute Bioprocess Measurement
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Solution Overview
Problem
Conventional monitoring methods for bio-manufacturing systems are prone to drift due to environmental factors and fail to provide comprehensive feedback on multiple product quality attributes, limiting effective control over process parameters.
Innovation Solution
A system featuring multiple chromatography columns and flow control devices, coupled with a control unit, to analyze biological samples for various product quality attributes such as concentration, aggregation, charge variants, and purity, allowing for precise adjustment of bio-manufacturing processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If multiple chromatography columns and analyzers are used to measure multiple product quality attributes, then measurement precision and reliability are improved, but device complexity increases
Solution Approach 1:
The system divides the analysis into multiple independent chromatography columns (e.g., CEX, SEC, RP-HPLC) and analyzers, each dedicated to measuring specific product quality attributes. This segmentation allows each component to be optimized for its specific function while collectively providing comprehensive quality assessment through controlled flow paths.
Solution Approach 2:
The flow control device serves multiple functions by dynamically directing sample flow to different chromatography columns and analyzers based on which product quality attributes need measurement. This single multi-functional component replaces what would otherwise require multiple dedicated flow paths, reducing overall system complexity while maintaining measurement capabilities.
2Manufacturing precision
If comprehensive product quality attribute analysis is performed, then manufacturing precision is improved, but loss of time increases due to multiple analysis steps
Solution Approach 1:
The system enables continuous analysis by processing different product quality attributes in sequence through multiple chromatography columns and analyzers without interrupting the overall analytical workflow. Sample portions are continuously directed through appropriate analysis paths, maintaining continuous useful action throughout the measurement process.
Solution Approach 2:
The system performs preliminary separation and analysis of different product quality attributes through dedicated chromatography columns before final evaluation. By pre-separating analytes using CEX, SEC, or RP-HPLC methods before detection, the system prepares samples in advance for specific measurements, reducing total analysis time while maintaining comprehensive quality assessment.
3Adaptability or versatility
If sample portions are directed through different analysis paths, then adaptability is improved, but device complexity increases due to flow control requirements
Solution Approach 1:
The flow control device is designed with dynamic capabilities to adjust flow paths in real-time based on which product quality attributes require measurement. Valves and flow directors can be reconfigured during operation to route sample portions through different chromatography columns and analyzers, providing adaptability while using a single integrated control mechanism rather than multiple fixed paths.
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
Enables accurate and comprehensive measurement of multiple product quality attributes, enhancing process control and product yield in continuous bio-manufacturing systems.
Implementation Method 1
The systems can include sample analyzers with different types of chromatography columns dedicated to the measurement of specific product quality attributes
Implementation Method 2
The first chromatography column can be a cation exchange chromatography column
Implementation Method 3
The first chromatography column can be a size exclusion chromatography column
Implementation Method 4
The first chromatography column can be a reversed phase chromatography column
Implementation Method 5
The sample purification device can include an affinity chromatography column
Implementation Method 6
The quantification detector can include a diode array detector, a spectrometric detector configured to measure absorbance information
Data Source
AI summary
Systems for measuring a product quality attribute of an analyte of a biological sample include a first flow control device, a sample purification device, a second flow control device in fluid communication with first and second sample analyzers, where the first sample analyzer includes a first chromatography column, and a control unit configured so that during operation of the system, the control unit adjusts a configuration of the second flow control device to direct a portion of the biological sample to one of the first and second sample analyzers, and determines a product quality attribute of an analyte of the biological sample based on an analysis of the portion of the biological sample by the one of the first and second sample analyzers.