Virus Inactivation Device for Liquid Chromatography

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Solution Overview

Problem

Current liquid chromatography systems for biomolecule separation require manual intervention and are not fully automated, especially in processes involving virus inactivation, which is time-consuming and labor-intensive, and there is a need for improved continuous processing methods.

Innovation Solution

A virus inactivation device and system that includes at least two containers with moveable sidewalls, allowing for continuous and automated processing by recycling fluid streams and using pH adjustments and UV light for virus inactivation, integrated with multi-column chromatography systems to reduce manual intervention and enhance processing efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If manual intervention is used for sample application and parameter changes in liquid chromatography systems, then operational flexibility is maintained, but processing time increases and labor intensity increases

Engineering Contradiction:
Improveprocessing speedVSAvoidautomation level
Core Design Contradiction:
ProductivityVSExtent of automation

Solution Approach 1:

The system is divided into multiple independent chromatography columns (first column, second column, third column) that can operate in parallel or sequence. Each column handles specific separation tasks, allowing continuous processing without manual intervention between steps. The fluid handling system is segmented into multiple loops enabling automated switching between columns and operations.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system implements continuous chromatographic separation by circulating fluid through multiple columns in an automated loop. The mobile phase continuously flows through the columns, and detected signals are continuously processed. This eliminates idle time between batch operations and maintains constant productive action throughout the system.

Inventive Principle:
Principle #20Continuity of useful action

2Reliability

If virus inactivation is performed using traditional chemical addition methods, then virus inactivation is achieved, but processing time increases and the process cannot be easily integrated into continuous flow systems

Engineering Contradiction:
Improvevirus inactivation efficacyVSAvoidinactivation time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The system replaces traditional chemical addition methods with a physical field-based approach using UV irradiation. UV light sources are positioned to irradiate the fluid as it flows through designated zones in the chromatography system, eliminating the need for chemical mixing and extended contact times while maintaining effective virus inactivation.

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

Solution Approach 2:

The system changes the method parameter from chemical concentration control to physical energy input (UV irradiation dose). By controlling the intensity and duration of UV exposure in the flow path, the system achieves virus inactivation without requiring the fluid to remain stationary for extended periods, enabling integration into continuous flow operations.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If multiple chromatography columns are used for rapid separation, then separation speed increases, but system complexity increases and integration of additional processing steps becomes more difficult

Engineering Contradiction:
Improveseparation speedVSAvoidsystem complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The chromatography system is designed with multi-functional capabilities where the same hardware infrastructure supports both rapid multi-column separation and virus inactivation operations. The fluid handling system, pumps, and detection apparatus serve dual purposes: performing chromatographic separations and delivering fluid through UV irradiation zones for virus inactivation, reducing overall system complexity despite multiple processing functions.

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

Solution Approach 2:

The system merges the virus inactivation function directly into the chromatography flow path by positioning UV light sources within or adjacent to the column housings and fluid channels. This integration eliminates separate inactivation chambers and complex interconnections, allowing rapid separation and virus inactivation to occur in a unified continuous process.

Inventive Principle:
Principle #5Merging (Combining)

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 fully automated and efficient virus inactivation and modification of biomolecules, reducing processing time and labor, while meeting regulatory requirements for bioprocesses, by using a continuous flow system with parallel containers that maintain fluid for a predetermined period for effective virus inactivation.

Implementation Method 1

using pH adjustments and UV light for virus inactivation

Methodology Applied
Scientific EffectUV light: Light

Implementation Method 2

The simpler modification of the fluid would include pH change and/or salt additions

Methodology Applied
Scientific EffectpH change:

Data Source

PatentEP3277397B1Virus inactivation device for a liquid chromatograhy system and corresponding method
Publication Date: 2024.06.19 CYTIVA SWEDEN AB
  • EP3277397B1 patent drawingFigure 1~2
  • EP3277397B1 patent drawingFigure 3~4
  • EP3277397B1 patent drawingFigure 5

AI summary

The present invention relates to a liquid chromatography system for the separation of bio-molecules in a fluid including at least two unit operations, wherein the first unit operation is a step of multi-column chromatography and the second unit operation is a step modifying said bio-molecules and/or the fluid, wherein the modification comprises feeding the fluid resulting from the last chromatography column of the first unit operation into a system comprising at least two containers, wherein each container has a volume and a moveable sidewall arranged to divide the volume into a first sub-volume and a second sub-volume, and each container comprises a first port connected to the first volume and a second port connected to the second sub-volume. The invention also relates to a virus inactivation device for a chromatography system according to the invention, which enables continuous or semi-continuous processing of biomolecules, as well as a method of using such a device.