Single-cell fucosylation breakdown: Switching fucose to europium

Fucosylation and its fucosidic linkage-specific motifs are believed to be essential to understand their distinct roles in cellular behavior, but their quantitative information has not yet been fully disclosed due to the requirements of ultra-sensitivity and selectivity. Herein, we report an approach that converts fucose (Fuc) to stable europium (Eu) isotopic mass signal on hard ionization inductively coupled plasma mass spectrometry (ICP-MS). Metabolically assembled azido-fucose on the cell surface allows us to tag them with an alkyne-customized Eu-crafted bacteriophage MS2 capsid nanoparticle for Eu signal multiplication, resulting in an ever lowest detection limit of 4.2 zmol Fuc. Quantitative breakdown of the linkage-specific fucosylation motifs in situ preserved on single cancerous HepG2 and paracancerous HL7702 cells can thus be realized on a single-cell ICP-MS platform, specifying their roles during the cancering process. This approach was further applied to the discrimination of normal hepatocellular cells and highly, moderately, and poorly differentiated hepatoma cells collected from real hepatocellular carcinoma tissues.