Multi-axis electromagnetic sample handler for live imaging of organoid structures and dynamics.

Abstract

Organoids are a flexible experimental model to explore countless human conditions. They can emulate essential physiological and pathological functions of an in vivo system. Acquiring three-dimensional (3D) images is critical but challenging in live organoid-based studies due to the complex structure of these samples. Imaging quality worsens in deeper microscopic planes because of light scattering. Furthermore, the imaging system introduces an unavoidable image distortion, the point spread function (PSF). Current methods to decrease these issues are often expensive, highly complex, limited to specific usage, or unsuitable for live organoid experiments. Increasing the freedom of movement within the microscope field of view for imaging organoid samples can minimize the light depth penetration limitation and the PSF distortion. To address this, we are developing an electromagnetic sample handler that will enable multi-axis rotation for high-resolution microscopy. We have also developed a complementary image reconstruction algorithm. Our initial results are promising, demonstrating that this sample handler provides a higher freedom of movement, can be integrated into existing imaging platforms, and has helped enable enhanced visualization of organoid structures.