Single-objective selective plane illumination microscopy for multi-well organoid imaging.

Abstract

Current preclinical in vitro and non-human animal models fail to adequately reproduce human physiology and disease processes. While recent efforts have focused on using microfluidics to help create stem cell-derived organoids as a way to better model 3D vascularization and improve the delivery of therapeutics, there remain challenges especially in terms of long-term imaging. To address this, we report here on the development of single-objective Selective Plane Illumination Microscopy (SoSPIM) for high-content imaging. This platform is capable of imaging samples in different mounting formats, ranging from tissue slices, to conventional culture dishes and and multi-well plates. To demonstrate this platform's capabilities, we imaged cerebral organoid slices and fixed organoids cultured in multi-well microfluidic devices. Our future work will focus on applying SoSPIM for long-term live organoid imaging using machine learning approaches for tracking and mapping intercellular dynamics and structures.