Drug testing of monodisperse arrays of live microdissected tumors using a valved multiwell microfluidic platform
Ethan Lockhart, Lisa F. Horowitz, A. D. Rodriguez, Songli Zhu, Tran Nguyen, Mehdi Mehrabi, Taranjit S. Gujral, Albert Folch
Abstract
based on patient-derived tumor organoids, require a growth step that alters the TME. On the other hand, microdissected tumors (μDTs) or "spheroids" that retain an intact TME have shown promising responses to immunomodulators acting on native immune cells. However, difficult tissue handling after microdissection has reduced the throughput of drug testing on μDTs, thereby constraining the inherent advantages of producing numerous TME-preserving units of tissue for drug testing. Here we demonstrate a microfluidic 96-well platform designed for drug treatment of hundreds of similarly-sized, cuboidal μDTs ("cuboids") produced from a single tumor sample. The platform organizes a monodisperse array of four cuboids per well in 384 hydrodynamic traps. The microfluidic device, entirely fabricated in thermoplastics, features 96 microvalves that fluidically isolate each well after the cuboid loading step for straightforward multi-drug testing. Since our platform makes the most of scarce tumor tissue, it can potentially be applied to human biopsies that preserve the human TME while minimizing animal testing.