Embedded-Electrode 3D Tissue Culture for Cardiotoxicity Screening
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Solution Overview
Problem
Existing 3D tissue culture platforms face challenges in scaling up to high-throughput testing due to complex fabrication processes and the need for functional readouts of cardiotoxicity, with current systems prone to device failure and drug absorption, and lacking robustness for cardiotoxicity screening.
Innovation Solution
A device with embedded electrodes and elastic sensing elements in a substrate, allowing for electrical stimulation and contractile force measurement, simulating a physiological environment and enabling scalable, automated tissue culture and non-invasive functional readouts.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If complex fabrication procedures are used to build hollow or suspended microstructures for 3D tissue culture, then tissue formation is promoted, but device complexity increases and scalability is reduced
Solution Approach 1:
The patent extracts the complex hollow microstructure fabrication step and replaces it with simple planar wells containing suspended microcarriers. This eliminates the need for building suspended microstructures while maintaining the ability to support 3D tissue formation through the microcarrier suspension approach.
Solution Approach 2:
The patent segments the tissue culture function into separate components: planar wells for containment, suspended microcarriers for 3D structure support, and embedded sensors for monitoring. This segmentation allows each component to be optimized independently and simplifies the overall fabrication process.
2Ease of operation
If PDMS posts are used as force sensors to measure contractile force, then noninvasive measurement is enabled, but device reliability decreases due to tissue slipping and drug absorption
Solution Approach 1:
The patent replaces the mechanical PDMS post system with an embedded sensor system that directly measures contractile force through force-sensitive resistors or strain gauges integrated into the well structure. This eliminates tissue slipping issues and removes drug absorption problems associated with PDMS.
Solution Approach 2:
The patent merges the force sensing function directly into the well structure through embedded sensors, eliminating the need for separate PDMS posts. This integration improves reliability by removing interfaces where tissue can slip while maintaining the measurement capability.
3Productivity
If conventional monolayer cultures are used for high-throughput screening, then productivity is improved, but measurement precision of cardiotoxicity decreases due to lack of tissue-level function
Solution Approach 1:
The patent creates a universal platform that combines high-throughput multi-well format with 3D tissue culture capability and integrated sensing. This allows the system to perform both high-throughput screening and precise cardiotoxicity measurement using the same platform, eliminating the trade-off between throughput and accuracy.
Solution Approach 2:
The patent uses composite structures combining planar well substrates with suspended microcarriers and embedded sensing elements. This composite approach enables simultaneous achievement of high-throughput format, 3D tissue organization, and precise functional measurement.
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
The device provides a scalable, automated platform for 3D tissue culture with embedded electrodes, facilitating high-throughput cardiotoxicity screening and reducing device failure, while maintaining tissue integrity and enabling precise electrical stimulation and force measurement.
Implementation Method 1
at least two elastic sensing elements disposed across the well such that there is a gap between the sensing elements and the bottom of the well, wherein the sensing elements are configured to: (a) permit attachment of the tissue formed therebetween, thereby suspending the tissue above the bottom of the well, and (b) deform in response to the contractile force exerted on the sensing elements by the tissue, thereby simulating a physiological environment that is native to the tissue and/or permitting measurement of the contractile force
Implementation Method 2
the pair of electrodes is configured to apply an electrical stimulation to the tissue
Data Source
AI summary
Embodiments described herein relate generally to devices, apparatuses, and systems with embedded electrodes for growing, maintaining, and/or using 3D tissues in vitro. The devices, apparatuses, and systems described herein can provide scalable, automated tissue stimulation.