UV Cell Pathlength Adaptation for Chromatography Breakthrough Monitoring

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Determining the operational status and binding capacities of chromatography columns is complex, especially in continuous chromatography systems where variability in feed concentration and flow rates complicates the measurement of breakthrough capacities, leading to inefficient process operation and potential product loss.

Innovation Solution

A method using UV detectors to continuously monitor the operational status of chromatography columns by calculating Delta signals from feed and effluent signals, allowing for real-time control and compensation for variations in column properties and feed composition, enabling dynamic control of the chromatography system.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional breakthrough capacity determination methods are used with fraction collection and subsequent HPLC analysis, then measurement accuracy can be achieved, but process complexity and time consumption increase significantly

Engineering Contradiction:
Improvebreakthrough capacity measurement accuracyVSAvoidprocess complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts the essential measurement function from the complex fraction collection and HPLC analysis process by implementing continuous UV detection directly in the effluent stream. This allows breakthrough capacity determination through real-time monitoring of UV absorbance signals, eliminating the need for manual fraction collection and subsequent laboratory analysis, thus reducing process complexity while maintaining measurement accuracy

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces the mechanical/manual process of fraction collection and HPLC analysis with an automated optical detection system using UV detectors. The continuous UV monitoring system automatically tracks solute concentration in the effluent, substituting the complex mechanical操作流程 with a streamlined optical measurement approach that reduces both device complexity and operational burden

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Productivity

If continuous monitoring of effluent concentration is implemented using UV detectors, then real-time breakthrough capacity determination is achieved, but measurement precision deteriorates when feed concentration varies randomly

Engineering Contradiction:
Improvereal-time monitoring capabilityVSAvoidbreakthrough capacity accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent implements feedback control by continuously comparing the effluent UV signal with the feed UV signal and using this information to adjust and determine breakthrough capacity in real-time. The system monitors the ratio between effluent and feed concentrations, allowing accurate breakthrough determination even when feed concentration varies, as the feedback mechanism compensates for these variations dynamically

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent changes the measurement parameter from absolute concentration values to the ratio or difference between effluent and feed UV signals. This parameter transformation makes the measurement robust against feed concentration variations, as the relative change in signals rather than absolute values is used to determine breakthrough capacity, maintaining precision under varying feed conditions

Inventive Principle:
Principle #35Parameter changes

3Productivity

If multiple columns are used in continuous chromatography with simultaneous operation, then productivity increases, but process control complexity increases

Engineering Contradiction:
Improveprocess efficiencyVSAvoidsystem complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent applies the same UV detection and control methodology universally across multiple chromatography columns operating in continuous mode. By using identical detection and control strategies for each column, the system achieves multi-functionality where a single control approach manages multiple columns simultaneously, increasing productivity without proportionally increasing control complexity

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent uses real-time UV signal parameters from each column to dynamically adjust operating conditions and determine optimal breakthrough points. By continuously monitoring and adjusting parameters such as flow rates and loading conditions based on UV feedback from multiple columns, the system maintains simplified control while achieving high productivity through coordinated multi-column operation

Inventive Principle:
Principle #35Parameter changes

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 enables reliable and dynamic monitoring and control of chromatography systems, ensuring optimal operation even with non-identical columns and varying feed conditions, reducing product losses and improving process efficiency.

Implementation Method 1

detecting the UV absorbance in the feed material

Methodology Applied
Scientific EffectUV absorbance: Absorption (EM radiation)

Data Source

PatentEP3586123B1Methods and systems for adapting pathlength and/or wavelength of a UV-absorbance cell in a chromatography system
Publication Date: 2023.03.08 CYTIVA SWEDEN AB
  • EP3586123B1 patent drawingFigure 1~2
  • EP3586123B1 patent drawingFigure 3
  • EP3586123B1 patent drawingFigure 4a~4c

AI summary

The present invention relates to a method for determining operational status of a chromatography column (1; 39, 47, 59; 107, 109, 111, 113), comprising detecting a feed signal (21; 201) representative of the composition of a feed material provided to the inlet of the column; detecting the UV absorbance in the feed material, detecting an effluent signal (23; 203, 205, 207, 209) representative of the composition of the effluent from the column; and using the feed signal and the effluent signal to determine operational status of the column. The feed signal is generated using a first UV detector having a first UV cell pathlength operating at a first UV wavelength and the effluent signal is generated using a second UV detector having a second UV cell pathlength operating at a second UV wavelength. The method further comprising determining a first threshold value based on the detected UV absorbance in the feed material, and selecting the first UV cell pathlength and/or first UV wavelength based on the first threshold value.