Chromatography Column Venting for Sterile Gas and Pressure Purging

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Solution Overview

Problem

Chromatography columns face challenges with trapped gas and pressure issues during gamma irradiation, which can disrupt fluid flow dynamics and increase the risk of contamination, necessitating a method to maintain sterility and separation performance.

Innovation Solution

A tubing and valve system is connected to pre-packed chromatography columns to create a closed system, allowing for sterilization and subsequent removal of gas bubbles and pressure through purging with sterile liquid, using a hydrophobic vent filter and check valve to ensure aseptic conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If gamma irradiation is applied to sterilize pre-packed chromatography columns, then sterility is achieved, but gas pockets and pressurization occur within the packed bed

Engineering Contradiction:
ImprovesterilityVSAvoidgas pockets and pressurization
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The system segments the column into multiple zones with inlet and outlet ports at different elevations, allowing gas pockets to be isolated and removed from specific regions without compromising the entire packed bed structure or sterility

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention extracts harmful gas pockets and excess pressure from the packed bed through dedicated outlet ports positioned at strategic elevations, separating the gas removal function from the main chromatography flow path while maintaining sterility

Inventive Principle:
Principle #2Taking out (Extraction)

2Ease of operation

If gas pockets are removed from the packed bed, then fluid flow dynamics are improved, but sterility may be compromised

Engineering Contradiction:
Improvefluid flow dynamicsVSAvoidsterility
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The system introduces an intermediary gas removal pathway through outlet ports and external tubing that allows gas extraction without direct intervention into the sterile packed bed, using the intermediary pathway to bridge gas removal and sterility maintenance

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention replaces mechanical disruption of the packed bed with a controlled pressure differential system that uses pneumatic principles to draw out gas pockets through outlet ports, substituting direct mechanical intervention with a softer pressure-based approach

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

3Manufacturing precision

If pressure is reduced from the packed bed, then chromatography performance is maintained, but contamination risk increases

Engineering Contradiction:
Improvechromatography performanceVSAvoidcontamination risk
Core Design Contradiction:
Manufacturing precisionVSObject-affected harmful factors

Solution Approach 1:

The system performs preliminary gas and pressure removal through outlet ports before initiating the chromatography run, eliminating harmful factors in advance while maintaining the sterile barrier, so that subsequent operation proceeds without contamination risk

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention employs disposable sterile connectors and tubing in the gas removal pathway that can be discarded after single use, eliminating the need to maintain sterility of reusable components during the gas removal process while preserving the sterile packed bed

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

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

The method effectively maintains chromatography flow path integrity and sterility, ensuring performance comparable to pre-irradiation values by removing trapped gases and pressure without breaching sterility, thus preventing contamination and flow disruptions.

Implementation Method 1

using a hydrophobic vent filter and check valve to ensure aseptic conditions

Methodology Applied
Scientific EffectHydrophobic effect: Hydrophobe

Implementation Method 2

allowing for sterilization and subsequent removal of gas bubbles and pressure through purging with sterile liquid

Methodology Applied
Scientific EffectGamma irradiation: Radiation

Data Source

PatentEP3684426B1Methods and systems for removing pressure and air from chromatography columns
Publication Date: 2025.01.01 REPLIGEN CORP
  • EP3684426B1 patent drawingFigure 1A
  • EP3684426B1 patent drawingFigure 1B
  • EP3684426B1 patent drawingFigure 1C

AI summary

Methods and systems for removing gases and/or pressure formed during the sterilization, e.g., the gamma irradiation, of prepacked chromatography systems (column plus attached tube and valve set) are described. The methods include purging the gas and/or pressure through specially designed tube and valve sets without breaching the sterility of the prepacked sterile chromatography system. The systems include a sterile or aseptic pre-packed chromatography column including a column having an inlet and an outlet, a tubing and valve set attached to the inlet and the outlet, and a pump configured to pump sterile or aseptic liquid from the fluid source along the tubing and valve set, into the column tube inlet and out of the column tube outlet along a first flow path, thereby removing any entrapped gas and/or pressure from the chamber.