Laminar Flow Bioreactor Bypass Mechanism for Shear Reduction

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Solution Overview

Problem

Existing bioreactors face limitations in reducing shear forces, which lead to high cell mortality and hinder the growth of large volumes of tissue, particularly due to inherent design issues that create turbulence and hydrodynamic shear, making it challenging to control cell growth and maintain tissue integrity.

Innovation Solution

A non-rotating bioreactor design that utilizes laminar flow to reduce shear forces, achieved through a cylindrical shape and a bypass mechanism with adjustable irises controlled by pressure sensors, allowing for optimal medium delivery and cell growth in three dimensions, mimicking a microgravity environment while preventing cell damage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If stirred methods or suspension bioreactors are used, then mass transfer is improved, but shear forces increase which limits the sizes of cultures and practical applications

Engineering Contradiction:
Improvecell culture volumeVSAvoidshear forces
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The bioreactor is divided into multiple parallel channels instead of using a single stirred tank. Each channel is a separate flow path where fluid moves laminarly past cell aggregates, segmenting the overall culture volume into many small, manageable flow paths that avoid high shear forces while maintaining total culture capacity

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention uses hydraulic principles by allowing fluid to flow through and around cell aggregates in a controlled laminar flow manner. The fluid dynamics are engineered so that flow separates smoothly around aggregates rather than creating turbulent mixing, using hydraulic principles to transport nutrients and remove waste without mechanical stirring

Inventive Principle:
Principle #29Pneumatics and hydraulics

2Object-affected harmful factors

If rotational reactors are used to mimic microgravity, then hydrodynamic shear is reduced, but the design cannot adequately control the growth of large amounts of cells in a scaffold

Engineering Contradiction:
Improvehydrodynamic shearVSAvoidcell growth control
Core Design Contradiction:
Object-affected harmful factorsVSProductivity

Solution Approach 1:

The system dynamically adjusts flow rates through each channel using independent flow control mechanisms. This allows the bioreactor to adapt flow conditions to match the growth state of cell aggregates, providing dynamic control over nutrient delivery and waste removal without requiring rotation

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The bioreactor incorporates sensors and control systems that monitor cell growth and adjust flow rates accordingly. This feedback mechanism enables precise control over the growth of large amounts of cells in scaffolds by adjusting hydraulic conditions based on actual biological state

Inventive Principle:
Principle #23Feedback

3Use of energy by stationary object

If air lift bioreactors are used, then energy input is reduced and oxygen transfer is improved, but tissue culture sizes and volumes cannot be adequately controlled

Engineering Contradiction:
Improveenergy inputVSAvoidtissue culture volume control
Core Design Contradiction:
Use of energy by stationary objectVSProductivity

Solution Approach 1:

The bioreactor segments the culture volume into multiple parallel channels with independent flow control. This segmentation enables precise control over tissue culture sizes and volumes by adjusting flow distribution across individual channels, while maintaining low energy input through passive laminar flow design

Inventive Principle:
Principle #1Segmentation

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 bioreactor effectively reduces shear stresses, enabling the growth of large volumes of tissue with reduced cell mortality, maintaining tissue integrity and promoting three-dimensional cell growth by ensuring laminar flow and controlled fluid distribution, thus overcoming the limitations of existing bioreactor designs.

Implementation Method 1

The laminar flow reduces turbulence and shear forces that otherwise impede the growth of the biological material. Laminar flow can also allow for the rapid exchange of nutrients and waste products.

Methodology Applied
Scientific EffectLaminar flow: Laminar Flow

Data Source

PatentUS9057044B2Laminar flow reactor
Publication Date: 2015.06.16 ISRAELOWITZ MEIR
  • US9057044B2 patent drawing
  • US9057044B2 patent drawing
  • US9057044B2 patent drawing

AI summary

The present invention describes a laminar flow bioreactor with improved laminar flow lines of fluids. The bioreactor housing defines a chamber adapted to receive a scaffold. An inlet aperture at one end of the chamber is in fluid communication with an outlet aperture at the opposite end of the chamber. A bypass mechanism selectively operable from an open position to a closed position consisting of an iris assembly directs a portion of fluid flowing through the chamber around the scaffold-receiving area. This bioreactor is inserted in a bioreactor system.