High throughput screening system for engineered cardiac tissues

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Drug Discovery

Background:

• Three dimensional engineered cardiac tissues (3D ECTs) are vital in vitro models for assessing drug cardiotoxicity.
• Current methods for measuring 3D ECT contractile forces are low-throughput, limiting their use in pharmaceutical development.
• Existing imaging techniques face tradeoffs between resolution, field of view, and speed, restricting the number of samples analyzed simultaneously.

Purpose of the Study:

• To develop and validate an innovative mosaic imaging system for high-throughput contractile force sensing of 3D ECTs.
• To overcome the limitations of conventional imaging in terms of speed, resolution, and field of view.
• To enable parallel, real-time monitoring of contractile forces in a 96-well plate format.

Main Methods:

• Design and construction of a novel mosaic imaging system.
• Seeding of 3D ECTs onto a 96-well plate.
• Validation of the system through real-time, parallel contractile force monitoring over three weeks.
• Pilot drug testing using isoproterenol.

Main Results:

• The mosaic imaging system successfully monitored contractile forces of 3D ECTs in parallel for up to three weeks.
• The system demonstrated the ability to perform pilot drug testing, showing its practical application.
• The throughput for contractile force sensing was increased to 96 samples per measurement.

Conclusions:

• The developed mosaic imaging tool significantly enhances the throughput of preclinical cardiotoxicity assays using 3D ECTs.
• This approach reduces the cost, time, and labor associated with drug safety testing.
• The mosaicking strategy offers a generalizable method for scaling up image-based screening in multi-well plate formats.