Electromechanically monitored engineered heart tissue platform

PROJECT SUMMARY - ABSTRACT Non-animal models for the evaluation of therapeutics represents an ideal for development of personalized approaches to treating a range of medical conditions, as recently emphasized by the FDA. Notably, human induced pluripotent stem cells (hiPSCs) can be created by reprogramming patient cells derived from a variety of sources, including blood, skin, and urine. These cells can then be differentiated into cardiomyocytes- like cells (hiPSC-CMs), which can be used to gain basic insight into heart diseases such genetic cardiomyopathies and to assess potential therapeutic strategies for heart disease. An electromechanically monitored engineered heart tissue (emEHT) platform was recently developed at Northwestern University through an interdisciplinary collaboration that allows for characterization of arrhythmia propensity using flexible electronics technology. Using the STTR mechanism, we now aim to commercialize this platform to allow for wider dissemination and use by the biomedical research and drug development community. Here, we will develop a consumable electronics fabrication process that meets prespecified design criteria (geometry, tissue load, strain sensor performance, and electrode impedance) and is compatible with device fabrication runs of 10s to 100s of devices per run to support high throughput study requirements. Next, we will design and build custom data acquisition and bioamplification equipment using integrated electronics that are specifically designed to assess emEHTs; intuitive software will communicate with the electronics and display the acquired data to the user. At each stage of development, we will work closely with the Fullenkamp Lab at Northwestern University who will serve as the real-world testbed for the emEHT platform. Prototype consumable electronics will be assessed using real world hiPSC-CM EHTs and feedback will be given to NeuroLux based on tissue performance and cell viability. The emEHT platform performance will be compared to available commercial EHT platforms and those used previously from the Rogers group. Importantly, the integrated electronics and user interface will be assessed in the real-world tissue culture environment. Assessment of the EHT response to well-studied prototypic pharmacologic agents will be performed to validate the platform’s ability to detect physiologically meaningful responses. This low-cost, manufacturable system will leverage the strengths of NeuroLux’s existing commercial platform currently in use worldwide to further advance physiological research capabilities.