High throughput screening system for engineered cardiac tissues

Marshall S Ma; Subramanian Sundaram; Lihua Lou; Arvind Agarwal; Christopher S Chen; Thomas G Bifano

doi:10.3389/fbioe.2023.1177688

High throughput screening system for engineered cardiac tissues

Front Bioeng Biotechnol. 2023 May 11:11:1177688. doi: 10.3389/fbioe.2023.1177688. eCollection 2023.

Authors

Marshall S Ma^{1

2}, Subramanian Sundaram³, Lihua Lou⁴, Arvind Agarwal⁴, Christopher S Chen³, Thomas G Bifano^{1

2}

Affiliations

¹ Mechanical Engineering, Boston University, Boston, MA, United States.
² Photonics Center, Boston University, Boston, MA, United States.
³ Biomedical Engineering, Boston University, Boston, MA, United States.
⁴ Mechanical and Materials Engineering, Florida International University, Miami, FL, United States.

Abstract

Introduction: Three dimensional engineered cardiac tissues (3D ECTs) have become indispensable as in vitro models to assess drug cardiotoxicity, a leading cause of failure in pharmaceutical development. A current bottleneck is the relatively low throughput of assays that measure spontaneous contractile forces exerted by millimeter-scale ECTs typically recorded through precise optical measurement of deflection of the polymer scaffolds that support them. The required resolution and speed limit the field of view to at most a few ECTs at a time using conventional imaging. Methods: 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: The system performance was validated through real-time, parallel contractile force monitoring for up to 3 weeks. Pilot drug testing was conducted using isoproterenol. Discussion: The described tool increases contractile force sensing throughput to 96 samples per measurement; significantly reduces cost, time and labor needed for preclinical cardiotoxicity assay using 3D ECT. More broadly, our mosaicking approach is a general way to scale up image-based screening in multi-well formats.

Keywords: PDMS; cardiotoxicity screening; engineered cardiac tissue; high throughput imaging(HTI); micro manufacturing.

Grants and funding

This research was supported by the NSF Engineering Research Center in Cellular Metamaterials (CELL-MET) under grant EEC-1647837. REU participant support was provided by the REU Site: Integrated Nanomanufacturing, NSF EEC-1852255.