Grooved Cardiomyocyte Membrane for Dynamic Cardiotoxicity Screening
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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 allows for out-of-plane deformation, simulating heart contractions and stretching, enabling the alignment of cardiomyocytes without the need for fibronectin patterns, and includes a multi-electrode structure for measuring electrical activity, facilitating the assessment of cardiotoxicity and electrophysiological responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If static model systems with human embryonic stem cell-derived cardiomyocytes are used, then cardiotoxicity testing can be performed, but the dynamic simulation of heart beating and exercise conditions is lost
Solution Approach 1:
The patent transforms static cardiomyocyte cultures into dynamic systems by introducing a deformable substrate that can be stretched and released cyclically to simulate heart beating. The substrate includes a deformable region with patterned grooves that mechanically stimulate the cardiomyocytes, enabling the model to replicate physiological conditions including exercise-induced stress and heart failure states.
2Adaptability or versatility
If complex bioreactors with stretchable silicone plates and gel-embedded cardiomyocytes are used, then mechanical stretching can be simulated, but device complexity increases and electrical activity measurement becomes difficult
Solution Approach 1:
The patent divides the substrate into distinct functional regions: a rigid region for structural support and electrode placement, and a deformable region with patterned grooves for mechanical stretching. This segmentation allows independent optimization of each region's function while simplifying the overall device architecture compared to fully complex bioreactors.
Solution Approach 2:
The substrate exhibits spatially varying mechanical properties, with the deformable region designed to stretch while the rigid region remains stable. The patterned grooves are localized to specific areas to guide cardiomyocyte alignment and stretching in critical zones, while other regions maintain different properties for support and measurement functions.
3Adaptability or versatility
If cardiomyocytes are embedded in gel layers on stretchable plates, then in vivo mechanical response can be simulated, but electrical activity measurement is prevented
Solution Approach 1:
The patent uses a thin deformable substrate that acts as both a mechanical stretching medium and an electrode support platform. The substrate's thin film structure allows electrical signals from embedded cardiomyocytes to be detected through multi-electrode arrays while still providing the necessary mechanical deformability to simulate heart beating conditions.
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 provides a reproducible and cost-effective means to simulate heart contractions and stretching, improving the detection of cardiotoxic effects and allowing for the maturation of cardiomyocytes, thereby enhancing the accuracy of cardiotoxicity testing and drug development.
Implementation Method 1
a deformable elastomer layer and patterned grooves allows for out-of-plane deformation, simulating heart contractions and stretching
Implementation Method 2
includes a multi-electrode structure for measuring electrical activity, facilitating the assessment of cardiotoxicity and electrophysiological responses
Data Source
Figure 1(a)~1(e)
Figure 1(f)~1(i)
Figure 1(j)~1(l)
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.