Bioreactor Actuator for Myocardial Slice Simulation

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Solution Overview

Problem

In vitro heart models, such as myocardial slices, face challenges in accurately replicating the mechanical and electrical events of the heart due to artificial environments, leading to artefacts and limited translational relevance, especially when studying cardiovascular research over extended periods.

Innovation Solution

A bioreactor apparatus with an actuator and sensor system that applies synchronized periodic mechanical and electrical stimuli to myocardial slices, mimicking the cardiac cycle, allowing for long-term study of heart tissue in a controlled, physiological environment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of stationary object

If heart tissue is kept in an artificial environment for prolonged periods of time (culture), then the study duration is extended, but the tissue properties change dramatically leading to minimal resemblance to in vivo heart

Engineering Contradiction:
Improvestudy durationVSAvoidtissue property fidelity
Core Design Contradiction:
Duration of action of stationary objectVSReliability

Solution Approach 1:

The patent applies parameter changes by dynamically adjusting mechanical parameters (stretching, compression, shear forces) and fluid flow parameters (flow rate, pressure gradients) to match in vivo cardiac conditions. This allows the tissue to experience physiological stimuli that maintain its native properties during prolonged culture periods.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements periodic action through cyclic mechanical stimulation protocols that replicate the heartbeat rhythm. The tissue is subjected to repeated cycles of stretching and relaxation, mimicking the cardiac cycle, which maintains the tissue's functional properties over extended periods.

Inventive Principle:
Principle #19Periodic action

2Device complexity

If in vitro heart models are used to study the heart in isolation, then the complexity problem is solved, but the model can only be reliably studied in the short-term

Engineering Contradiction:
Improvesystem complexityVSAvoidstudy duration
Core Design Contradiction:
Device complexityVSDuration of action of stationary object

Solution Approach 1:

The patent segments the complex in vivo heart system into isolated myocardial slices that can be cultured in controlled in vitro environments. This segmentation allows the tissue to be studied in isolation while maintaining relevance through appropriate mechanical and fluid stimulation protocols.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent ensures continuity of useful action by implementing continuous fluid flow through the tissue samples and sustained mechanical stimulation protocols. This continuous physiological stimulation prevents tissue degradation and maintains functional properties throughout the study duration.

Inventive Principle:
Principle #20Continuity of useful action

3Device complexity

If crude mechanical stretching protocols are used with electrodes to beat myocardial slices, then the model is simplified, but the relevance of the model and its ability to translate findings is minimized

Engineering Contradiction:
Improveprotocol complexityVSAvoidtranslational relevance
Core Design Contradiction:
Device complexityVSReliability

Solution Approach 1:

The patent applies parameter changes by using physiological ranges of mechanical stress (0.1-10% strain), fluid flow rates (0.1-10 mL/min), and pressure gradients that match in vivo conditions. These optimized parameters enhance the translational relevance of the simplified in vitro model.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements feedback mechanisms through force sensors that measure tissue contraction forces and flow sensors that monitor blood flow rates. This feedback allows real-time adjustment of stimulation parameters to maintain physiological conditions, enhancing the model's translational relevance.

Inventive Principle:
Principle #23Feedback

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 approach enables the simulation of in vivo conditions, maintaining the archetypical properties of heart tissue, enhancing the predictive capacity of cardiovascular research and allowing for extended studies without artificial changes, thus improving the translational impact of findings.

Implementation Method 1

an actuator coupling to enable the actuator rod to be connected for applying mechanical force to a tissue sample mounted in the container

Methodology Applied
Scientific EffectMechanical Force: Mechanical Force

Implementation Method 2

The base of the reactor vessel may be thermally conductive, and the walls of the container may be thermally insulating. For example the base may comprise a metal such as stainless steel and the walls may comprise a polymer such as PEEK.

Methodology Applied
Scientific EffectThermal conduction: Conduction (thermal)

Implementation Method 3

the walls of the container may be thermally insulating

Methodology Applied
Scientific EffectThermal insulation: Thermal Insulation

Implementation Method 4

The apparatus may comprise a sensor, such as a force transducer, for sensing mechanical force. This mechanical force sensor may be arranged for sensing mechanical force generated by the tissue sample

Methodology Applied
Scientific EffectForce sensing: Force

Implementation Method 5

The container may comprise an inlet for flow of liquid into the container from the recirculation system, and an outlet for the flow of liquid out of the container into the recirculation system

Methodology Applied
Scientific EffectFluid flow:

Data Source

PatentUS20220396753A1Bioreactor apparatus and method for in-vitro heart simulation
Publication Date: 2022.12.15 IMPERIAL COLLEGE INNVOATIONS LTD
  • US20220396753A1 patent drawing
  • US20220396753A1 patent drawing
  • US20220396753A1 patent drawing

AI summary

An apparatus comprising an actuator for moving an actuator rod and a bioreactor vessel is disclosed herein. The bioreactor vessel comprises a container for holding a liquid, a mounting for mounting a tissue sample in the container, and, an actuator coupling to enable the actuator rod to be connected for applying mechanical force to the tissue sample. The apparatus also comprises a seat, fixed with respect to the actuator and configured for locating the reactor vessel in a location selected so that the actuator can be connected for applying said force via the actuator coupling. The reactor vessel is removable from the apparatus.