Collaborated with Prof. Chenguang Wang in Jilin University, we have rationally designed a new Nile Red derivative, NR-11, which exhibits significantly improved LDs specificity and photostability. Utilizing this new LDs probe, we have successfully conducted various advanced fluorescence imaging, e.g. time-lapse three-dimensional (3D) confocal imaging of cells, time-lapse 3D dynamic tracking of a single LD with 3D-SMART, and two-photon 3D imaging of tissues. These advanced imaging results not only demonstrate the utility of this new fluorescent probe but also provide novel insights into the cell biology study of LDs.