Stacked Bioreactor Carriers for Uniform Cell Culture Flow

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Solution Overview

Problem

Current cell culture methods for stem cells are inefficient and damage-sensitive, particularly due to mechanical stresses and external influences, and existing bioreactors are not optimized for stem cell growth, leading to suboptimal surface area utilization and inefficient nutrient distribution.

Innovation Solution

A bioreactor design featuring a stack of carriers with open spaces for fluid interconnection between levels, allowing for even distribution of liquid medium and cell adherence, while minimizing mechanical stress and optimizing surface area for cell growth, using carriers with non-overlapping open spaces to ensure uniform flow and prevent vertical medium flow.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If stem cells are cultured in stationary conditions in tissue culture flasks, then cell culture is simple to operate, but surface area per unit volume is inefficient and cell expansion is time-consuming

Engineering Contradiction:
Improveease of operationVSAvoidproductivity
Core Design Contradiction:
Ease of operationVSProductivity

Solution Approach 1:

The invention transitions from two-dimensional stationary culture in flat flasks to three-dimensional stacked carrier configuration. Multiple carriers are stacked vertically to create multiple culture levels within a compact volume, dramatically increasing the surface area available for cell culture per unit volume while maintaining ease of operation through a modular stack design that can be handled as a single unit.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The culture system is segmented into multiple discrete carriers stacked in a vertical configuration. Each carrier provides an independent culture surface, and the segmented structure allows for efficient space utilization while enabling parallel culture of multiple cell batches simultaneously, thereby increasing overall productivity without complicating the operation.

Inventive Principle:
Principle #1Segmentation

2Quantity of substance

If liquid medium is distributed in stacked carriers with open spaces, then nutrient and oxygen supply is uniform, but device complexity increases

Engineering Contradiction:
Improvenutrient and oxygen supplyVSAvoiddevice complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The stacked carrier design enables self-service fluid distribution where the liquid medium naturally flows through the open spaces between carriers via gravity and capillary action. This passive flow mechanism ensures uniform nutrient and oxygen supply to all culture levels without requiring complex pumping systems or active control mechanisms, thereby achieving enhanced substance distribution while minimizing device complexity.

Inventive Principle:
Principle #25Self-service

3Productivity

If carriers have open spaces for fluid flow, then liquid medium distribution is efficient, but mechanical strength of carriers is reduced

Engineering Contradiction:
Improveliquid medium distribution efficiencyVSAvoidmechanical strength
Core Design Contradiction:
ProductivityVSStrength

Solution Approach 1:

The carriers are designed with a porous or perforated structure containing open spaces that facilitate efficient liquid medium distribution throughout the stack. These porous features allow uniform fluid flow and nutrient penetration while the overall carrier geometry and material selection maintain sufficient mechanical strength to support the stacked configuration and withstand handling operations.

Inventive Principle:
Principle #31Porous materials

4Quantity of substance

If multiple T-flasks are used to produce sufficient cells, then cell quantity is adequate, but preparation time and operational steps increase

Engineering Contradiction:
Improvecell quantityVSAvoidpreparation time
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

Multiple culture surfaces that would traditionally require separate T-flasks are merged into a single integrated stacked carrier assembly. This consolidation allows sufficient cell quantity to be produced in one unified device, eliminating the need to manually fill and manage multiple separate flasks, thereby dramatically reducing preparation time and operational steps while maintaining adequate cell output.

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

This design enables cost-effective, high-quality cell culture with improved growth conditions for stem cells and primary cells by ensuring uniform nutrient and oxygen supply, reducing mechanical stress, and facilitating efficient harvesting.

Implementation Method 1

The levels are fluidly interconnected via one or more open spaces in the carriers so that the liquid medium can flow from one level to an adjacent level

Methodology Applied
Scientific EffectFluid flow through open spaces:

Implementation Method 2

The one or more open spaces between a first and a second level adjacent to the first level do not overlap with each other

Methodology Applied
Scientific EffectUniform flow distribution:

Implementation Method 3

a plurality of carriers for cell adherence and liquid medium distribution

Methodology Applied
Scientific EffectCell adherence to surface:

Data Source

PatentEP2516618B1Bioreactor for cell culture
Publication Date: 2020.07.08 PALL ARTELIS
  • EP2516618B1 patent drawingFigure 1~2
  • EP2516618B1 patent drawingFigure 3~4
  • EP2516618B1 patent drawingFigure 5~6

AI summary

A bioreactor (1) for the culture of cells (C) comprising a stack of carriers (7) for cell (C) adherence and liquid medium (M) distribution. The carriers (7) are stacked so as to define levels (6) between adjacent carriers (7) for the flow of the liquid medium (M). Adjacent levels (6) are fluidly interconnected via open spaces (2) so that the liquid medium (M) can flow from one level (6) to an adjacent level (6). The open spaces (2) between a first and an adjacent second level (6') do not overlap with the one or more open spaces (2) between the second level (6') and an adjacent third level (6''). One or more of the carriers may also include an area adapted to prevent cell adhesion or growth, thereby allowing for the viewing of cell growth on adjacent carriers from a vantage point external to the bioreactor. Related methods are also disclosed.