Multiplexed detection technology has been attractive for its simultaneous assay of several analytes, which play significant roles in applications such as screening for combinatorial chemistry, genetic analysis, and clinical diagnostics. This work reports a novel and potentially powerful encoding system based upon dispersible suspension arrays of multilayer rare earth core/shell nanoparticles that are capable of multiplexed, high-sensitivity reporting for biomolecule detection by the Z-contrast imaging. These nanobarcode arrays are encoded by nanostructure design based on different atomic numbers. With the well-resolved high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) decoding technique, many thousands of unique nanobarcodes can be identified by multilayer core/shell nanostructure. Their applications to multiplexed biodetection of DNA demonstrated the highly sensitive (picomole) features of this novel nanobarcode system.