Non-Invasive and Minute-Frequency 3D Tomographic Imaging Enabling Long-Term Spatiotemporal Observation of Single Cell Fate

Non-invasive and rapid imaging technique at subcellular resolution is significantly important for multiple biological applications such as cell fate study. Label-free refractive-index (RI)-based 3D tomographic imaging constitutes an excellent candidate for 3D imaging of cellular structures, but its full potential in long-term spatiotemporal cell fate observation is locked due to the lack of an efficient integrated system. Here, a long-term 3D RI imaging system incorporating a cutting-edge white light diffraction phase microscopy module with spatiotemporal stability, and an acoustofluidic device to roll and culture single cells in a customized live cell culture chamber is reported. Using this system, 3D RI imaging experiments are conducted for 250 cells and demonstrate efficient cell identification with high accuracy. Importantly, long-term and frequency-on-demand 3D RI imaging of K562 and MCF-7 cancer cells reveal different characteristics during normal cell growth, drug-induced cell apoptosis, and necrosis of drug-treated cells. Overall, it is believed that the proposed 3D tomographic imaging technique opens up a new avenue for visualizing intracellular structures and will find many applications such as disease diagnosis and nanomedicine.

Automated summary

Non-invasive and rapid imaging technique at subcellular resolution is significantly important for multiple biological applications. This study presents a long-term 3D refractive-index imaging system that integrates a cutting-edge white light diffraction phase microscopy module and an acoustofluidic device for single cell culture. The system allows efficient cell identification and enables long-term and frequency-on-demand 3D imaging of cancer cells, providing insights into cell growth, apoptosis, and necrosis. Overall, the proposed imaging technique opens up new avenues for visualizing intracellular structures and has potential applications in disease diagnosis and nanomedicine.