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Real time optical imaging methods for single molecule and single particle tracking are mainly dominated by fluorescence microscopy,but the inherent photobleaching and photoblinking of dye molecules greatly hinder their long time accuracy and reproducibility.A promising alternate is to use the plasmonic metal nanoparticles(MNPs)as the single molecule probes,whose spectral characteristics can be readily manipulated based on their unique size,shape and composition dependent optical properties.Compared with traditional organic dye molecules,the absorption and scattering cross-sections of MNPs are several orders of magnitude larger.Specially,they are highly photostable,allowing individual MNPs to be tracked continuously for extended period of time with no photobleaching,photoblinking,or photosaturation.Herein,we present improved optical scattering imaging apparatus and methods for detection of single MNPs and tracking their translational and rotational motions in living cells.Our methods could be widely applied to study important biological activities with single MNPs as optical contrast agents,and to investigate cell-nanoparticle interactions for efficient gene and drug delivery.