Optical tomography reconstructing 3D motion and structure of multiple-scattering samples under rotational actuation

Optical diffraction tomography (ODT) has emerged as a powerful tool for imaging biological cells in a non-invasive and label-free manner. However, conventional approaches using ODT by varying the illumination are plagued by the missing cone problem, which introduces ambiguity and deteriorates the axial resolution in the reconstruction. Although utilizing object rotation has the potential to yield an isotropic resolution, experimental control or prior retrieval of the rotational parameters is challenging. In this work, we demonstrate the ODT of multiple-scattering samples undergoing variable rotational motion, unlocking the potential for isotropic resolution in non-contact systems. We introduce a comprehensive reconstruction method to jointly retrieve both the sample and the rotational motion in 3D. An interferometric setup enables the recording of amplitude and phase data while the object is rotated in a non-contact manner around one or more chosen axes in an acoustofluidic device. We evaluate the tomographic reconstruction performance of the method for clusters of micro-beads and highlight its suitability for biomedical applications beyond single cells, demonstrating high-resolution reconstruction of dense cancer spheroids containing more than 100 cells.