Integrated Bioreactor System for Multi-Stimulus Cell Culture Control

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Solution Overview

Problem

Existing bioreactors are unable to simultaneously combine mechanical, electrical, and magnetic stimulation, and lack integrated control systems for real-time monitoring of these stimuli, limiting their effectiveness in cell and tissue engineering applications.

Innovation Solution

An integrated bioreactor system with a computational platform for controlling and optimizing mechanical, electrical, and magnetic stimuli, featuring a plurality of electrodes/coils for adaptable stimulation and real-time monitoring, along with machine learning for continuous process improvement.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If multiple types of stimuli (mechanical, electrical, magnetic) are applied simultaneously, then the effectiveness of cell and tissue engineering is improved, but the device complexity increases

Engineering Contradiction:
Improveeffectiveness of cell and tissue engineeringVSAvoiddevice complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines multiple stimulation systems (mechanical perfusion, electrical stimulation via electrodes, and magnetic stimulation via coils) into a single integrated bioreactor device. This merging allows simultaneous application of different stimuli types without requiring separate devices, thereby improving engineering effectiveness while managing complexity through integration.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The bioreactor is designed with multi-functionality to perform mechanical perfusion, electrical stimulation, and magnetic stimulation within a single device. This universal design enables the device to address multiple cell stimulation needs simultaneously, improving the overall effectiveness of tissue engineering applications.

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

2Manufacturing precision

If real-time monitoring and control systems are integrated, then the optimization of stimulation parameters is improved, but the device complexity increases

Engineering Contradiction:
Improveoptimization of stimulation parametersVSAvoiddevice complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent incorporates real-time monitoring systems with sensors that continuously measure stimulation parameters and cell responses. This feedback mechanism allows the control system to optimize stimulation parameters dynamically, improving manufacturing precision in terms of parameter control while managing complexity through automated feedback loops.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The integrated control system automatically adjusts and optimizes stimulation parameters based on real-time data from sensors and monitoring devices. This self-service capability reduces the need for manual intervention and complex external control systems, thereby improving parameter optimization while managing overall device complexity.

Inventive Principle:
Principle #25Self-service

3Adaptability or versatility

If multiple electrodes and coils are used for adaptable stimulation, then the versatility of the bioreactor is improved, but the device complexity increases

Engineering Contradiction:
Improveversatility of the bioreactorVSAvoiddevice complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The bioreactor employs multiple discrete electrodes and coils that can be independently controlled and activated. This segmentation allows the system to provide adaptable stimulation by activating specific components as needed, improving versatility while managing complexity through modular, independent elements rather than a monolithic system.

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

Enables efficient cell proliferation and differentiation by mimicking native biological conditions, allowing for real-time control and optimization of stimulation parameters, thereby enhancing tissue regeneration processes.

Implementation Method 1

external component (2), comprising an external surface (21) with a plurality of electrodes and/or coils (22)

Methodology Applied
Scientific EffectElectrical stimulation: Electric Field

Implementation Method 2

external component (2), comprising an external surface (21) with a plurality of electrodes and/or coils (22)

Methodology Applied
Scientific EffectMagnetic stimulation: Magnetic Field

Implementation Method 3

integrated bioreactor system, which allows the optimization of the application of mechanical, electrical, and magnetic stimuli

Methodology Applied
Scientific EffectMechanical stimulation: Mechanical Force

Data Source

PatentEP4112714A1Integrated bioreactor system and process for control, learning and monitoring of cell culture using the same
Publication Date: 2023.01.04 INST POLITECNICO DE LEIRIA
  • EP4112714A1 patent drawingFigure 1~2
  • EP4112714A1 patent drawingFigure 3~4
  • EP4112714A1 patent drawingFigure 5

AI summary

The present invention describes an integrated bioreactor system (1), which comprises an external component (2), an internal component (3) and a support structure (4) which comprises a computational platform for control, learning and optimization of stimuli application. The present invention further describes a process for the control, learning and monitoring of cell culture using the referred integrated bioreactor system (1), which allows the optimization of the application of different stimuli to cells placed in three-dimensional models (36) located in the internal component (3), to mimic the native conditions of the biological tissue. This invention solves the problems referring to the need to optimize, control and monitor, in real time, the parameters involved in the stimulation of different cells in tissue engineering applications, thus reducing the time involved in differentiation and / or proliferation process, that are parameterizable for different cell lines.