Cardiomyocyte Membrane Array for Dynamic Cardiac Electrophysiology
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Solution Overview
Problem
Current in vitro cell-based models for drug development are inadequate in detecting cardiotoxic side effects, particularly QT interval prolongation, and lack the dynamic simulation of a beating heart, making them unsuitable for predicting drug-induced arrhythmias and cardiac issues.
Innovation Solution
A device with a deformable elastomer layer and patterned grooves for aligning cardiomyocytes, allowing out-of-plane deformation and simulating heart contractions, enabling the measurement of electrophysiological responses to chemical compounds while reducing complexity and cost.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If cardiomyocytes are embedded in a gel layer on a stretchable silicone plate to simulate mechanical response, then the device can simulate heart contraction dynamics, but the device complexity increases and electrical activity measurement becomes difficult
Solution Approach 1:
The patent extracts cardiomyocytes from the gel matrix and places them directly on the stretchable silicone plate surface. This removal of the gel embedding layer simplifies the device structure while preserving the ability to simulate heart contraction dynamics, and crucially enables direct electrical activity measurement without interference from the gel medium
Solution Approach 2:
The stretchable silicone plate serves multiple functions: it provides mechanical stretching to simulate heart contraction dynamics, supports direct cardiomyocyte attachment for electrical recording, and enables both physiological and pathophysiological condition simulation. This multi-functionality reduces overall device complexity by consolidating multiple roles into a single component
2Measurement precision
If cardiomyocytes are cultured on standard multi-electrode arrays, then electrical activity can be measured, but the model system remains static and cannot simulate the dynamics of the beating heart
Solution Approach 1:
The patent introduces dynamic stretching capability to the multi-electrode array system by using a stretchable silicone plate that can be cyclically deformed to simulate heart contraction. This transforms the static culture system into a dynamic model that replicates the beating heart environment while maintaining electrical recording functionality
Solution Approach 2:
The patent changes the physical state of the culture substrate from rigid to elastomeric, allowing it to undergo cyclic deformation. This parameter change enables the system to simulate physiological stretching conditions during heart contraction while preserving the electrical measurement capability through integrated electrodes
3Reliability
If in-vivo animal studies are used for cardiotoxicity evaluation, then comprehensive cardiac function assessment is possible, but the cost increases and ethical challenges arise
Solution Approach 1:
The patent creates a simplified in vitro copy of the in-vivo heart environment by using stretchable substrates that replicate mechanical contraction dynamics. This copied model system provides reliable cardiotoxicity evaluation data without requiring actual animal subjects, thereby reducing cost and ethical burden while maintaining evaluation accuracy
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 device facilitates accurate in vitro cardiac electrophysiology screening, allowing for the detection of cardiotoxic effects and the simulation of both physiological and pathophysiological heart conditions, improving the prediction of drug safety and reducing the need for costly animal studies.
Implementation Method 1
a deformable elastomer layer extending over said cavity, wherein a portion of said elastomer layer covers said cavity
Implementation Method 2
an adhesive coating; and a plurality of cardiomyocytes adhered to said coating and assembled in at least some of said grooves
Data Source
AI summary
Disclosed is a device (100) for cardiac electrophysiology screening comprising a substrate (10) comprising a cavity (42), said substrate carrying a deformable layer (32) extending over said cavity (42), wherein a portion of said deformable layer (32) covers said cavity and acts as a membrane over said cavity (32), said portion having a surface comprising a pattern of grooves (44) and carrying a multi-electrode structure (110, 110′); and a plurality of cardiomyocytes (130) assembled in at least some of said grooves (44). A method of manufacturing such a device (100) is also disclosed.