Isotropic imaging-based contactless manipulation for single-cell spatial heterogeneity analysis

Isotropic imaging of single cells is crucial in single-cell research on cellular heterogeneity, organelle communication, and biophysical cell characterization. Isotropic imaging is extremely challenging due to the limited spatial sampling frequency of conventional microscopes and anisotropy in 3D point spread functions. Herein, an overview of various contactless manipulation methods in single-cell isotropic imaging, including optical, acoustic, electrical, magnetic, and fluidic methods, is presented. In addition, the advantages and disadvantages of these methods when combined with different imaging modalities are discussed. Moreover, the spatial resolution, sample throughput, cellular viability, and application scenarios are reviewed to help researchers select the optimal single-cell isotropic imaging method for the intended application. Finally, the prospects of isotropic imaging are highlighted.