Predicting patient’s response to cancer immunotherapy requires highly sensitive and multiplexed assay of cellular biomarkers. Many bio-markers of cancer cells are expressed at low levels at the early-stage, which makes the multiplexed detection difficult. Flow cytometry is commonly employed to analysis low abundance of biomarkers, but overlapping emission spectra of fluorophores restricts their use in highly multiplexed experiments. Mass cytometry is an innovative technology designed to address multiplexing limitation of flow cytometry by using heavy metal isotopes as tags. As the spectra of the metal is narrow, this technology enables simultaneous measurement of over 40 markers per cell. However, one of the major drawbacks of mass cytometry is a lack of sensitivity due to the low signal intensity of conventional metal chelating polymers (MCPs). Here, we introduce nanotechnology into mass cytometry by coupling sub-20 nm nanoparticles (containing >10000 lanthanide ions) with monoclonal antibodies (mAbs) to increase the detection sensitivity by 100-fold.