Clarifying intact 3D tissues on a microfluidic chip for high-throughput structural analysis

Yih Yang Chen, Pamuditha N Silva, Abdullah Muhammad Syed, Shrey Sindhwani, Jonathan V Rocheleau, Warren CW Chan

PNAS December 27, 2016 113 (52) 14915-14920 | DOI: 10.1073/pnas.1609569114


Structural analysis of microscale three-dimensional tissues (3D microtissues) in high-throughput is becoming increasingly important in drug discovery, regenerative medicine, and other biomedical areas because they recapitulate many in vivo biological features not present in 2D models. This can be done by using microfluidic technology to control and apply external forces to on-chip 3D microtissues, and imaging these organ-on-chip systems with confocal microscopy. However, the high cellular density of 3D microtissues scatters light and fundamentally limits the ability to characterize the entire tissue construct. We developed an on-chip strategy to rapidly clarify, image, and analyze whole intact microtissues without compromising internal structures. Our technique removes the imaging depth limit, allowing accurate analysis and characterization of entire tissues in microfluidic chips.