Cardiotoxicity Assessment through a Polymer-Based Cantilever Platform: An Integrated Electro-Mechanical Screening...

Area of Science:

• Cardiovascular Research
• Drug Discovery and Development
• Biomedical Engineering

Background:

• Traditional preclinical cardiac toxicity screening relies on electrophysiology (e.g., microelectrode arrays - MEA), which may not capture all drug effects.
• Assessing only field potential duration (FPD) is insufficient as drugs have diverse mechanisms of action.
• Existing platforms lack simultaneous measurement of both electrophysiology and contractility.

Purpose of the Study:

• To develop and validate a novel, non-invasive platform for comprehensive preclinical cardiotoxicity evaluation.
• To enable simultaneous real-time monitoring of cardiomyocyte electrical activity and contraction force.
• To improve the accuracy of cardiac safety profiling for diverse drug mechanisms.

Main Methods:

• A novel platform featuring eight cantilevers with strain sensors and MEA for simultaneous measurement.
• Real-time monitoring of cardiomyocyte contraction force (detecting ≈2 µN) and field potential signals.
• Utilizing the same cardiomyocytes for both electrophysiological and contractility measurements.

Main Results:

• The platform successfully detected drug-induced toxicity profiles for six drugs with varied mechanisms.
• It accurately identified toxicity even for drugs not affecting potassium channels.
• Demonstrated capability for sensitive detection of cardiac contraction force and field potential.

Conclusions:

• The developed platform offers a comprehensive, non-invasive method for assessing drug-induced cardiotoxicity.
• This innovative approach enhances preclinical cardiac function assessment.
• Poised to significantly advance the field of preclinical cardiotoxicity screening.