Deformable Cell-Like Microlasers for Real-Time Mechanical Quantification in Organoids

Abstract Mechanical stress in multicellular environments plays a critical role in a wide range of tissue function and drug delivery. However, conventional methods are incapable of quantifying internal solid stress in situ , which is the hallmark of the 3D multicellular mechanical environment. To overcome the limitations, here we developed hollow-core structured microsphere lasers to realize all-optical direct recording of cellular stress in organoids and spheroids with cellular resolution. The deformations of whispering-gallery-mode laser can therefore be transduced into the change of the laser spectrum to reflect deformation within two-hundred nanometers in deep tissue environment. Our findings demonstrate the capability to quantify internal solid stress in different types of human tumor spheroids in real time. We also explored its potential in mechano-responded drug screening. Dynamic monitoring of contractile stress inside human embryonic stem cell-derived cardiac organoids was also obtained. This method may bring new opportunities to mechanobiology with multicellular resolution and accelerate high-throughput drug screening in human organoids.