Chromatography Bubble Trap with Permanent Opening for Degassing

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Solution Overview

Problem

Conventional preparative HPLC systems face challenges in transferring gradient formation and process conditions to different dimensions and designs, with gas liberation during eluent gradient formation affecting NIR measurements and column integrity, and existing bubble traps inadequately degas eluents due to pressure constraints.

Innovation Solution

A chromatography system with a bubble trap having a permanent opening at its highest point, allowing adjustable degassing and excess liquid removal, and featuring two NIR detectors for continuous gradient monitoring and column integrity assessment, enabling flexible operation across various column dimensions and designs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional bubble traps under pressure are used, then the mixing circuit can maintain pressure, but the bubble traps cannot fulfil a complete degassing function

Engineering Contradiction:
Improvedegassing functionVSAvoidpressure in bubble trap
Core Design Contradiction:
ReliabilityVSStress or pressure

Solution Approach 1:

The system separates the bubble trap from the high-pressure mixing circuit by introducing a depressurization device. This segmentation allows the bubble trap to operate at low pressure for effective degassing, while the mixing circuit maintains high pressure for proper gradient formation. The bubble trap and mixing circuit are divided into independent pressure zones.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

A depressurization device acts as an intermediary between the high-pressure mixing circuit and the low-pressure bubble trap. This intermediary component enables pressure transition, allowing eluent to be depressurized before entering the bubble trap for degassing, then repressurized before returning to the mixing circuit.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If gradient formation is controlled only by pump delivery volumes, then pump operation is simple, but volume contraction effects are not taken into consideration

Engineering Contradiction:
Improvegradient controlVSAvoidgradient accuracy
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The system incorporates NIR detectors that continuously monitor the actual gradient formation in the mixing circuit. This feedback information is used to detect and compensate for volume contraction effects, ensuring accurate gradient delivery despite changes in eluent composition and temperature.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The system replaces purely mechanical pump-based gradient control with an optical measurement system (NIR detection). This substitution enables real-time monitoring and compensation of volume contraction effects that cannot be detected by mechanical means alone.

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

3Stability of the object's composition

If gas is liberated during gradient formation, then eluent composition changes, but NIR measurement upstream of the column is adversely affected

Engineering Contradiction:
Improveeluent compositionVSAvoidNIR measurement
Core Design Contradiction:
Stability of the object's compositionVSMeasurement precision

Solution Approach 1:

The system performs preliminary degassing of the eluent in the bubble trap before the eluent enters the mixing circuit and undergoes gradient formation. By removing dissolved gases in advance, the system prevents gas liberation during gradient formation that would interfere with NIR measurements.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The bubble trap extracts and removes dissolved gases from the eluent through continuous degassing. This extraction of harmful gas components prevents their interference with subsequent NIR measurements and gradient formation processes.

Inventive Principle:
Principle #2Taking out (Extraction)

4Reliability

If conventional preparative HPLC systems are built individually for certain dimensions, then each system is optimized for specific dimensions, but gradient formation is not transferable to different dimensions

Engineering Contradiction:
Improvesystem optimizationVSAvoidgradient transferability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The system introduces universal components including a bypass line with flow meter and control valve that can be used across different system configurations and dimensions. The NIR monitoring and feedback control mechanism provides a universal method for ensuring gradient accuracy regardless of system scale.

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

Solution Approach 2:

The system enables parameter adjustment and scaling by incorporating controllable valves and flow meters in the bypass line. This allows gradient parameters to be modified and optimized for different column dimensions while maintaining the same underlying gradient formation mechanism.

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 solution ensures reproducible and stable gradient formation, improved column robustness, and continuous monitoring of system and column quality, allowing for timely adjustments and maintenance, thereby enhancing process reliability and quality.

Implementation Method 1

the liberation of gas dissolved in the eluent during gradient formation

Methodology Applied
Scientific EffectGas liberation: Cavitation

Implementation Method 2

one upstream of the chromatography column and one downstream of the chromatography column

Methodology Applied
Scientific EffectNIR measurement: Absorption Spectroscopy

Data Source

PatentEP2776825B1Preparative column chromatography system
Publication Date: 2024.06.19 F HOFFMANN LA ROCHE & CO AG
  • EP2776825B1 patent drawingFigure 1
  • EP2776825B1 patent drawingFigure 2
  • EP2776825B1 patent drawingFigure 3

AI summary

A chromatography system comprising a mixing circuit or a mixing chamber, a bubble trap, a concentration detector and one or more pumps, characterized in that the bubble trap has a permanent opening at its highest point is described herein. Furthermore, a chromatography system is described, characterized in that it contains two concentration detectors the first of which is located in the mixing circuit or the mixing chamber and the second is located downstream of the main pump.