MechE PhD Dissertation Defense: Shendu Marshall Ma

TITLE: High Throughput Screening System for Engineered Cardiac Tissue

ABSTRACT: Three dimensional engineered cardiac tissues (3D ECTs) have become indispensable for in vitro screening to assess drug cardiotoxicity, a leading cause of failure in pharmaceutical development. A current bottleneck is the relatively low throughput of such assays, which infer spontaneous contractile forces exerted by millimeter-scale ECTs through precise optical measurement of deflection of the polymer scaffolds that support them. The required resolution and speed restrain the field of view to at most a few ECTs at a time using conventional imaging. To balance the inherent tradeoff among imaging resolution, field of view and speed, an innovative mosaic imaging system was designed, built, and validated to sense contractile force of 3D ECTs seeded on a 96- well plate. Results have shown real-time, parallel contractile force monitoring for up to 3 weeks. Pilot drug testing was conducted using isoproterenol. A parallel molding process was also developed to fabricate the compliant ECT scaffolds in a 96-wellplate, significantly reducing cost and labor associated with the current one-by-one molding process. Work in progress involves development of parallel electrical pacing and fluorescent imaging, allowing electrophysiological characterization of ECTs in conjunction with the contractile characterization in the 96-well plate format. Future work will focus on optimization of the ECT seeding process for the 96-wellplate. The dissertation provides a scale-up prototype for the entire workflow of cardiotoxicity testing with ECTs including scaffold molding, tissue seeding and functional assay. Outcome of this dissertation is partially or fully licensable with confirmed interests from industrial and government sources. The engineering work encompassed in this dissertation could contribute to the high throughput translational use of other types of engineered tissues.

COMMITTEE: ADVISOR Professor Thomas Bifano, ME/BME/ECE/MSE; CHAIR Professor Keith Brown, ME/MSE/Physics; Professor Alice White, ME/BME/MSE/Physics; Professor Andre Sharon, ME/MSE; Professor Emma Lejeune, ME