Foldable Mixing Element for Reduced Shear Stress in Cell Culture

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Solution Overview

Problem

Current bioreactors face limitations in scalability, mixing efficiency, cellular shear stress, oxygen mass transfer, and large laboratory footprints, particularly at larger scales, due to mechanical constraints and design limitations.

Innovation Solution

A collapsible cell culture vessel with a flexible portion and a foldable mixing element, optimized for reduced shear stress and varying volumetric ranges, featuring a polymeric sheet material and a sweep area ratio designed to minimize cellular damage and enhance mixing efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional rigid impellers are used for mixing, then mixing efficiency is improved, but cellular shear stress increases causing cellular damage

Engineering Contradiction:

Improvemixing efficiencyVSAvoidcellular shear stress

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent employs a flexible membrane impeller composed of thin film material that can bend and deform during rotation. This flexibility allows the impeller to move with the fluid rather than forcing rigid rotation, significantly reducing shear stress on cells while maintaining effective mixing through the membrane's ability to displace and circulate the culture medium.

Inventive Principle:

Principle #30Flexible shells and thin films

Solution Approach 2:

The patent changes the physical state and mechanical properties of the mixing element from rigid to flexible. By transforming the impeller material properties and operational characteristics (from fixed-speed rigid rotation to flexible variable deformation), the system achieves gentle mixing that preserves cell integrity while maintaining mixing efficiency.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If multiple impellers are used to improve mixing, then mixing efficiency is improved, but device complexity and manufacturing cost increase

Engineering Contradiction:

Improvemixing efficiencyVSAvoidnumber of impellers

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The flexible membrane impeller is divided into multiple segmented sections or zones along its length, each capable of independent deformation and fluid displacement. This segmentation allows a single impeller structure to perform the mixing function that would traditionally require multiple rigid impellers, reducing overall device complexity while maintaining mixing efficiency.

Inventive Principle:

Principle #1Segmentation

3Device complexity

If wave-mixed bioreactors are used, then device complexity is reduced, but scalability is limited due to mechanical constraints

Engineering Contradiction:

Improvemixing system complexityVSAvoidscalability

Core Design Contradiction:

Device complexityVSAdaptability or versatility

Solution Approach 1:

The patent replaces the external mechanical rocking platform system with an internal flexible membrane impeller driven by a magnetic coupling mechanism. This substitution eliminates the need for large external rockers and complex mechanical linkages, allowing the system to scale more easily while maintaining the simplified mixing approach of wave-like motion.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

4Productivity

If the bioreactor is designed for large scale, then productivity is improved, but oxygen mass transfer becomes limiting

Engineering Contradiction:

Improveproduction scaleVSAvoidoxygen mass transfer

Core Design Contradiction:

ProductivityVSQuantity of substance

Solution Approach 1:

The flexible membrane impeller generates dynamic fluid motion and turbulence through its oscillating and bending motion, creating enhanced gas-liquid interface renewal and improved oxygen mass transfer. The vibrational and pulsating flow patterns generated by the flexible membrane increase the effective surface area for gas exchange, overcoming the mass transfer limitations typically encountered in large-scale bioreactors.

Inventive Principle:

Principle #18Mechanical vibration

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 collapsible system reduces cellular shear stress, improves mixing efficiency, and allows for scalable operations with reduced laboratory footprint, while maintaining effective oxygen mass transfer and cellular growth support.

Implementation Method 1

a foldable portion disposed within the flexible portion for mixing the cell culture... optimized for reduced shear stress... a sweep area ratio designed to minimize cellular damage and enhance mixing efficiency

Methodology Applied

Scientific EffectFluid motion and shear stress: Shear Stress

Data Source

PatentUS12258549B2Systems and methods for a collapsible chamber with foldable mixing element

Publication Date: 2025.03.25 LIFE TECHNOLOGIES CORP

AI summary

The present set of embodiments relate to a system, method, and apparatus for culturing cells within a cell culture vessel having a mixing element. The cell culture system includes a flexible portion and a mixing element disposed therein. The mixing element includes a suspended foldable portion. The system is configured to reduce shear stress on cells without compromising mixing efficiency. This reduction is accomplished by using a mixing element having a large surface area allowing for reduced rotational speeds. The system is collapsible for ease of transport and disposal. The flexible portion collapses and the foldable portion folds to minimize the volume of the system while not in operation.